Metal alloys for medical devices

ABSTRACT

A medical device that is at least partially formed of a novel metal alloy, which novel metal alloy improves the physical properties of the medical device.

The present invention is a continuation-in-part of U.S. patentapplication Ser. No. 11/282,461 filed Nov. 18, 2005 entitled “MetalAlloy for a Stent” which claims priority on U.S. Provisional ApplicationSer. No. 60/694,891 filed Jun. 29, 2005 entitled “Improved Metal Alloysfor Medical Devices”, all of which are incorporated herein by reference.

The present invention is also a continuation-in-part of U.S. patentapplication Ser. No. 11/282,376 filed Nov. 18, 2005 entitled “MetalAlloy for a Stent, which is incorporated herein by reference.

The present invention also a claims priority on U.S. ProvisionalApplication Ser. Nos. 60/658,226 filed Mar. 3, 2005 entitled “ImprovedMetal Alloys for Medical Devices”; 60/694,881 filed Jun. 29, 2005entitled “Improved Metal Alloys for Medical Devices”; and 60/739,688filed Nov. 23, 2005 entitled “Process for Forming an Improved MetalAlloy Stent”, all of which are incorporated herein by reference.

The invention relates generally to medical devices, and particularly toa medical device that is at least partially formed of a novel molybdenumand rhenium metal alloy, and more particularly to a graft that is atleast partially formed of a novel molybdenum and rhenium metal and whichgraft is coating with one or more biological agents for use in treatinga body passageway.

BACKGROUND OF THE INVENTION

Medical treatment of various illnesses or diseases commonly includes theuse of one or more medical devices. Two types of medical device that arecommonly used to repair various types of body passageways are anexpandable graft or stent, or a surgical graft. These devices have beenimplanted in various areas of the mammalian anatomy. One purpose of astent is to open a blocked or partially blocked body passageway. When astent is used in a blood vessel, the stent is used to open the occludedvessel to achieve improved blood flow which is necessary to provide forthe anatomical function of an organ. The procedure of opening a blockedor partially blocked body passageway commonly includes the use of one ormore stents in combination with other medical devices such as, but notlimited to, an introducer sheath, a guiding catheter, a guide wire, anangioplasty balloon, etc.

Various physical attributes of a stent can contribute directly to thesuccess rate of the device. These physical attributes includeradiopacity, hoop strength, radial force, thickness of the metal,dimensions of the metal and the like. Cobalt and chromium and stainlesssteel are commonly used to form stents. These materials are commonlyused since such materials having a known history of safety,effectiveness and biocompatibility. These materials however have limitedphysical performance characteristics as to size, strength, weight,bendability, biostability and radiopacity.

The present invention can be generally directed to a medical device suchas, but not limited to, a stent that is at least partially formed of anovel metal alloy that improves the physical properties of the medicaldevice thereby improving the success rate of such medical device.

SUMMARY OF THE INVENTION

The present invention is generally directed to a medical device that isat least partially made of a novel metal alloy having improvedproperties as compared to past medical devices. The novel metal alloyused to at least partially form the medical device improves one or moreproperties (e.g., strength, durability, hardness, biostability,bendability, coefficient of friction, radial strength, flexibility,tensile strength, tensile elongation, longitudinal lengthening,stress-strain properties, improved recoil properties, radiopacity, heatsensitivity, biocompatibility, etc.) of such medical device. These oneor more improved physical properties of the novel metal alloy can beachieved in the medical device without having to increase the bulk,volume and/or weight of the medical device, and in some instances theseimproved physical properties can be obtained even when the volume, bulkand/or weight of the medical device is reduced as compared to medicaldevices that are at least partially formed from traditional stainlesssteel or cobalt and chromium alloy materials. The novel metal alloy thatis used to at least partially form the medical device can thus 1)increase the radiopacity of the medical device, 2) increase the radialstrength of the medical device, 3) increase the yield strength and/orultimate tensile strength of the medical device, 4) improve thestress-strain properties of the medical device, 5) improve the crimpingand/or expansion properties of the medical device, 6) improve thebendability and/or flexibility of the medical device, 7) improve thestrength and/or durability of the medical device, 8) increase thehardness of the medical device, 9) improve the longitudinal lengtheningproperties of the medical device, 10) improved the recoil properties ofthe medical device, 11) improve the friction coefficient of the medicaldevice, 12) improve the heat sensitivity properties of the medicaldevice, 13) improve the biostability and/or biocompatibility propertiesof the medical device, and/or 14) enable smaller, thinner and/or lighterweight medical devices to be made. The medical device generally includesone or more materials that impart the desired properties to the medicaldevice so as to withstand the manufacturing processes that are needed toproduce the medical device. These manufacturing processes can include,but are not limited to, laser cutting, etching, crimping, annealing,drawing, pilgering, electroplating, electro-polishing, chemicalpolishing, cleaning, pickling, ion beam deposition or implantation,sputter coating, vacuum deposition, etc.

In one non-limiting aspect of the present invention, a medical devicethat can include the novel metal alloy is a stent for use in a bodypassageway; however, it can be appreciated that other types of medicaldevices could be at least partially formed from the novel metal alloy.As used herein, the term “body passageway” is defined to be anypassageway or cavity in a living organism (e.g., bile duct, bronchioletubes, nasal cavity, blood vessels, heart, esophagus, trachea, stomach,fallopian tube, uterus, ureter, urethra, the intestines, lymphaticvessels, nasal passageways, eustachian tube, acoustic meatus, etc.). Thetechniques employed to deliver the medical device to a treatment areainclude, but are not limited to, angioplasty, vascular anastomoses,interventional procedures, and any combinations thereof. For vascularapplications, the term “body passageway” primarily refers to bloodvessels and chambers in the heart. The stent can be an expandable stentthat is expandable by a balloon and/or other means. The stent can havemany shapes and forms. Such shapes can include, but are not limited to,stents disclosed in U.S. Pat. Nos. 6,206,916 and 6,436,133; and all theprior art cited in these patents. These various designs andconfigurations of stents in such patents are incorporated herein byreference.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device is generally designed to include at leastabout 25 weight percent of the novel metal alloy; however, this is notrequired. In one non-limiting embodiment of the invention, the medicaldevice includes at least about 40 weight percent of the novel metalalloy. In another and/or alternative non-limiting embodiment of theinvention, the medical device includes at least about 50 weight percentof the novel metal alloy. In still another and/or alternativenon-limiting embodiment of the invention, the medical device includes atleast about 60 weight percent of the novel metal alloy. In yet anotherand/or alternative non-limiting embodiment of the invention, the medicaldevice includes at least about 70 weight percent of the novel metalalloy. In still yet another and/or alternative non-limiting embodimentof the invention, the medical device includes at least about 85 weightpercent of the novel metal alloy. In a further and/or alternativenon-limiting embodiment of the invention, the medical device includes atleast about 90 weight percent of the novel metal alloy. In still afurther and/or alternative non-limiting embodiment of the invention, themedical device includes at least about 95 weight percent of the novelmetal alloy. In yet a further and/or alternative non-limiting embodimentof the invention, the medical device includes about 100 weight percentof the novel metal alloy.

In still another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy that is used to form all or part of themedical device 1) is not clad, metal sprayed, plated and/or formed(e.g., cold worked, hot worked, etc.) onto another metal, or 2) does nothave another metal or metal alloy metal sprayed, plated, clad and/orformed onto the novel metal alloy. It will be appreciated that in someapplications, the novel metal alloy of the present invention may beclad, metal sprayed, plated and/or formed onto another metal, or anothermetal or metal alloy may be plated, metal sprayed, clad and/or formedonto the novel metal alloy when forming all or a portion of a medicaldevice.

In yet another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy that is used to form all or a portionof the medical device includes rhenium and molybdenum. The novel alloycan include one or more other metals such as, but not limited to,calcium, chromium, cobalt, copper, gold, iron, lead, magnesium, nickel,niobium, platinum, rare earth metals, silver, tantalum, titanium,tungsten, yttrium, zinc, zirconium, and/or alloys thereof.

In still another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy that is used to form all or a portionof the medical device is a novel metal alloy that includes at leastabout 90 weight percent molybdenum and rhenium. In one non-limitingcomposition, the content of molybdenum and rhenium in the novel metalalloy is at least about 95 weight percent. In another and/or alternativenon-limiting composition, the content of molybdenum and rhenium in thenovel metal alloy is at least about 97 weight percent. In still anotherand/or alternative non-limiting composition, the content of molybdenumand rhenium in the novel metal alloy is at least about 98 weightpercent. In yet another and/or alternative non-limiting composition, thecontent of molybdenum and rhenium in the novel metal alloy is at leastabout 99 weight percent. In still yet another and/or alternativenon-limiting composition, the content of molybdenum and rhenium in thenovel metal alloy is at least about 99.5 weight percent. In a furtherone non-limiting composition, the content of molybdenum and rhenium inthe novel metal alloy is at least about 99.9 weight percent. In still afurther and/or alternative non-limiting composition, the content ofmolybdenum and rhenium in the novel metal alloy is at least about 99.95weight percent. In yet a further and/or alternative non-limitingcomposition, the content of molybdenum and rhenium in the novel metalalloy is at least about 99.99 weight percent. As can be appreciated,other weight percentages of the rhenium and molybdenum content of thenovel metal alloy can be used. In one non-limiting composition, thepurity level of the novel metal alloy is such so as to produce a solidsolution of the novel metal alloy. A solid solution or homogeneoussolution is defined as a metal alloy that includes two or more primarymetals and the combined weight percent of the primary metals is at leastabout 95 weight percent, typically at least about 99 weight percent,more typically at least about 99.5 weight percent, even more typicallyat least about 99.8 weight percent, and still even more typically atleast about 99.9 weight percent. A primary metal is a metal component ofthe metal alloy that is not a metal impurity. A solid solution of anovel metal alloy that includes rhenium and molybdenum as the primarymetals is an alloy that includes at least about 95-99 weight percentrhenium and molybdenum. It is believed that a purity level of less than95 weight percent molybdenum and rhenium adversely affects one or morephysical properties of the metal alloy that are useful or desired informing and/or using a medical device. In one embodiment of theinvention, the rhenium content of the novel metal alloy in accordancewith the present invention is at least about 40 weight percent. In onenon-limiting composition, the rhenium content of the novel metal alloyis at least about 45 weight percent. In still another and/or alternativenon-limiting composition, the rhenium content of the novel metal alloyis about 45-50 weight percent. In yet another and/or alternativenon-limiting composition, the rhenium content of the novel metal alloyis about 47-48 weight percent. In still yet another and/or alternativenon-limiting composition, the rhenium content of the novel metal alloyis about 47.6-49.5 weight percent. As can be appreciated, other weightpercentages of the rhenium content of the novel metal alloy can be used.In another and/or alternative embodiment of the invention, themolybdenum content of the novel metal alloy in accordance with thepresent invention is at least about 40 weight percent. In onenon-limiting composition, the molybdenum content of the novel metalalloy is at least about 45 weight percent. In another and/or alternativenon-limiting composition, the molybdenum content of the novel metalalloy is at least about 50 weight percent. In still another and/oralternative non-limiting composition, the molybdenum content of thenovel metal alloy is about 50-60 percent. In yet another and/oralternative non-limiting composition, the molybdenum content of thenovel metal alloy is about 50-56 weight percent. As can be appreciated,other weight percentages of the molybdenum content of the novel metalalloy can be used.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the novel metal alloy that is used to form all or aportion of the medical device is a novel metal alloy that includes atleast about 90 weight percent molybdenum and rhenium, and at least oneadditional metal which includes titanium, yttrium, and/or zirconium. Theaddition of controlled amounts of titanium, yttrium, and/or zirconium tothe molybdenum and rhenium alloy has been found to form a metal alloythat has improved physical properties over a metal alloy thatprincipally includes molybdenum and rhenium. For instance, the additionof controlled amounts of titanium, yttrium, and/or zirconium to themolybdenum and rhenium alloy can result in 1) an increase in yieldstrength of the alloy as compared to a metal alloy that principallyincludes molybdenum and rhenium, 2) an increase in tensile elongation ofthe alloy as compared to a metal alloy that principally includesmolybdenum and rhenium, 3) an increase in ductility of the alloy ascompared to a metal alloy that principally includes molybdenum andrhenium, 4) a reduction in grain size of the alloy as compared to ametal alloy that principally includes molybdenum and rhenium, 5) areduction in the amount of free carbon, oxygen and/or nitrogen in thealloy as compared to a metal alloy that principally includes molybdenumand rhenium, and/or 6) a reduction in the tendency of the alloy to formmicro-cracks during the forming of the alloy into a medical device ascompared to the forming of a medical device from a metal alloy thatprincipally includes molybdenum and rhenium. In one non-limitingcomposition, the content of molybdenum and rhenium and the at least oneadditional metal in the novel metal alloy is at least about 90 weightpercent. In another and/or alternative non-limiting composition, thecontent of molybdenum and rhenium and the at least one additional metalin the novel metal alloy is at least about 95 weight percent. In stillanother and/or alternative non-limiting composition, the content ofmolybdenum and rhenium and the at least one additional metal in thenovel metal alloy is at least about 98 weight percent. In yet anotherand/or alternative non-limiting composition, the content of molybdenumand rhenium and the at least one additional metal in the novel metalalloy is at least about 99 weight percent. In still yet another and/oralternative non-limiting composition, the content of molybdenum andrhenium and the at least one additional metal in the novel metal alloyis at least about 99.5 weight percent. In a further one non-limitingcomposition, the content of molybdenum and rhenium and the at least oneadditional metal in the novel metal alloy is at least about 99.9 weightpercent. In still a further and/or alternative non-limiting composition,the content of molybdenum and rhenium and the at least one additionalmetal in the novel metal alloy is at least about 99.95 weight percent.In yet a further and/or alternative non-limiting composition, thecontent of molybdenum and rhenium and the at least one additional metalin the novel metal alloy is at least about 99.99 weight percent. As canbe appreciated, other weight percentages of the content of molybdenumand rhenium and the at least one additional metal in the novel metalalloy can be used. In one non-limiting composition, the purity level ofthe novel metal alloy is such so as to produce a solid solution of arhenium and molybdenum and the at least one additional metal. A solidsolution of a novel metal alloy that includes rhenium and molybdenum andthe at least one additional metal of titanium, yttrium and/or zirconiumas the primary metals is an alloy that includes at least about 95-99weight percent rhenium and molybdenum and the at least one additionalmetal. It is believed that a purity level of less than 95 weight percentmolybdenum and rhenium and the at least one additional metal adverselyaffects one or more physical properties of the metal alloy that areuseful or desired in forming and/or using a medical device. In oneembodiment of the invention, the rhenium content of the novel metalalloy in accordance with the present invention is at least about 40weight percent. In one non-limiting composition, the rhenium content ofthe novel metal alloy is at least about 45 weight percent. In stillanother and/or alternative non-limiting composition, the rhenium contentof the novel metal alloy is about 45-50 weight percent. In yet anotherand/or alternative non-limiting composition, the rhenium content of thenovel metal alloy is about 47-48 weight percent. As can be appreciated,other weight percentages of the rhenium content of the novel metal alloycan be used. In another and/or alternative embodiment of the invention,the molybdenum content of the novel metal alloy is at least about 40weight percent. In one non-limiting composition, the molybdenum contentof the novel metal alloy is at least about 45 weight percent. In anotherand/or alternative non-limiting composition, the molybdenum content ofthe novel metal alloy is at least about 50 weight percent. In stillanother and/or alternative non-limiting composition, the molybdenumcontent of the novel metal alloy is about 50-60 percent. In yet anotherand/or alternative non-limiting composition, the molybdenum content ofthe novel metal alloy is about 50-56 weight percent. As can beappreciated, other weight percentages of the molybdenum content of thenovel metal alloy can be used. The combined content of titanium, yttriumand zirconium in the novel metal alloy is less than about 5 weightpercent, typically no more than about 1 weight percent, and moretypically no more than about 0.5 weight percent. A higher weight percentcontent of titanium, yttrium and/or zirconium in the novel metal alloycan begin to adversely affect the brittleness of the novel metal alloy.When titanium is included in the novel metal alloy, the titanium contentis typically less than about 1 weight percent, more typically less thanabout 0.6 weight percent, even more typically about 0.05-0.5 weightpercent, still even more typically about 0.1-0.5 weight percent. As canbe appreciated, other weight percentages of the titanium content of thenovel metal alloy can be used. When zirconium is included in the novelmetal alloy, the zirconium content is typically less than about 0.5weight percent, more typically less than about 0.3 weight percent, evenmore typically about 0.01-0.25 weight percent, still even more typicallyabout 0.05-0.25 weight percent. As can be appreciated, other weightpercentages of the zirconium content of the novel metal alloy can beused. When titanium and zirconium are included in the novel metal alloy,the weight ratio of titanium to zirconium is about 1-10:1, typicallyabout 1.5-5:1, and more typically about 1.75-2.5:1. When yttrium isincluded in the novel metal alloy, the yttrium content is typically lessthan about 0.3 weight percent, more typically less than about 0.2 weightpercent, and even more typically about 0.01-0.1 weight percent. As canbe appreciated, other weight percentages of the yttrium content of thenovel metal alloy can be used. The inclusion of titanium, yttrium and/orzirconium in the novel metal alloy is believed to result in a reductionof oxygen trapped in the solid solution of the novel metal alloy. Thereduction of trapped oxygen enables the formation of a smaller grainsize in the novel metal alloy and/or an increase in the ductility of thenovel metal alloy. The reduction of trapped oxygen in the novel metalalloy can also increase the yield strength of the novel metal alloy ascompared to alloys of only molybdenum and rhenium (i.e., 2-10%increase). The inclusion of titanium, yttrium and/or zirconium in thenovel metal alloy is also believed to cause a reduction in the trappedfree carbon in the novel metal alloy. The inclusion of titanium, yttriumand/or zirconium in the novel metal alloy is believed to form carbideswith the free carbon in the novel metal alloy. This carbide formation isalso believed to improve the ductility of the novel metal alloy and toalso reduce the incidence of cracking during the forming of the metalalloy into a medical device (e.g., stent, etc.). As such, the novelmetal alloy exhibits increased tensile elongation as compared to alloysof only molybdenum and rhenium (i.e., 1-8% increase). The inclusion oftitanium, yttrium and/or zirconium in the novel metal alloy is alsobelieved to cause a reduction in the trapped free nitrogen in the novelmetal alloy. The inclusion of titanium, yttrium and/or zirconium in thenovel metal alloy is believed to form carbo-nitrides with the freecarbon and free nitrogen in the novel metal alloy. This carbo-nitrideformation is also believed to improve the ductility of the novel metalalloy and to also reduce the incidence of cracking during the forming ofthe metal alloy into a medical device (e.g., stent, etc.). As such, thenovel metal alloy exhibits increased tensile elongation as compared toalloys of only molybdenum and rhenium (i.e., 1-8% increase). Thereduction in the amount of free carbon, oxygen and/or nitrogen in thenovel metal alloy is also believed to increase the density of the novelmetal alloy (i.e., 1-5% increase). The formation of carbides,carbo-nitrides, and/or oxides in the novel metal alloy results in theformation of dispersed second phase particles in the novel metal alloy,thereby facilitating in the formation of small grain sizes in the metalalloy.

In still another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy includes less than about 5 weightpercent other metals and/or impurities. A high purity level of the novelmetal alloy results in the formation of a more homogeneous alloy, whichin turn results in a more uniform density throughout the novel metalalloy, and also results in the desired yield and ultimate tensilestrengths of the novel metal alloy. The density of the novel metal alloyis generally at least about 12 gm/cc, and typically at least about13-13.5 gm/cc. This substantially uniform high density of the novelmetal alloy significantly improves the radiopacity of the novel metalalloy. In one non-limiting composition, the novel metal alloy includesless than about 1 weight percent other metals and/or impurities. Inanother and/or alternative non-limiting composition, the novel metalalloy includes less than about 0.5 weight percent other metals and/orimpurities. In still another and/or alternative non-limitingcomposition, the novel metal alloy includes less than about 0.4 weightpercent other metals and/or impurities. In yet another and/oralternative non-limiting composition, the novel metal alloy includesless than about 0.2 weight percent other metals and/or impurities. Instill yet another and/or alternative non-limiting composition, the novelmetal alloy includes less than about 0.1 weight percent other metalsand/or impurities. In a further and/or alternative non-limitingcomposition, the novel metal alloy includes less than about 0.05 weightpercent other metals and/or impurities. In still a further and/oralternative non-limiting composition, the novel metal alloy includesless than about 0.02 weight percent other metals and/or impurities. Inyet a further and/or alternative non-limiting composition, the novelmetal alloy includes less than about 0.01 weight percent other metalsand/or impurities. As can be appreciated, other weight percentages ofthe amount of other metals and/or impurities in the novel metal alloycan exist.

In yet another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy includes a certain amount of carbon andoxygen. These two elements have been found to affect the formingproperties and brittleness of the novel metal alloy. The controlledatomic ratio of carbon and oxygen in the novel metal alloy also can beused to minimize the tendency of the novel metal alloy to formmicro-cracks during the forming of the novel alloy into a medicaldevice, and/or during the use and/or expansion of the medical device ina body passageway. In one non-limiting embodiment of the invention, thenovel metal alloy includes up to about 200 ppm carbon and up to about150 ppm oxygen. Higher carbon and oxygen contents in the novel metalalloy are believed to adversely affect one or more physical propertiesof the metal alloy that are useful or desired in forming and/or using amedical device. In one non-limiting formulation, the novel metal alloyincludes up to about 150 ppm carbon. In still another and/or alternativenon-limiting formulation, the novel metal alloy includes up to about 100ppm carbon. In yet another and/or alternative non-limiting formulation,the novel metal alloy includes less than about 50 ppm carbon. In stillyet another and/or alternative non-limiting formulation, the novel metalalloy includes up to about 100 ppm oxygen. In a further and/oralternative non-limiting formulation, the novel metal alloy includes upto about 75 ppm oxygen. In still a further and/or alternativenon-limiting formulation, the novel metal alloy includes up to about 50ppm oxygen. In yet a further and/or alternative non-limitingformulation, the novel metal alloy includes up to about 30 ppm oxygen.In still yet a further and/or alternative non-limiting formulation, thenovel metal alloy includes less than about 20 ppm oxygen. In yet afurther and/or alternative non-limiting formulation, the novel metalalloy includes less than about 10 ppm oxygen. As can be appreciated,other amounts of carbon and/or oxygen in the novel metal alloy canexist. In another and/or alternative non-limiting embodiment of theinvention, the carbon to oxygen atomic ratio in the novel metal alloy isgenerally at least about 2:1 (i.e., weight ratio of about 1.5:1). Thecontrol of the atomic ratio of carbon to oxygen in the novel metal alloyallows for the redistribution of oxygen in the metal alloy so as tominimize the tendency of micro-cracking in the novel metal alloy duringthe forming of the novel alloy into a medical device, and/or during theuse and/or expansion of the medical device in a body passageway. Whenthe carbon to oxygen atomic ratio falls below 2-2.5:1 (i.e., weightratio of about 1.5-1.88:1), the degree of elongation of the novel metalalloy decreases and the incidence of micro-cracking increases, thusadversely affecting one or more physical properties of the metal alloythat are useful or desired in forming and/or using the medical device.In one non-limiting formulation, the carbon to oxygen atomic ratio inthe novel metal alloy is generally at least about 2.5:1 (i.e., weightratio of about 1.88:1). In another and/or alternative non-limitingformulation, the carbon to oxygen atomic ratio in the novel metal alloyis generally at least about 3:1 (i.e., weight ratio of about 2.25:1). Instill another and/or alternative non-limiting formulation, the carbon tooxygen atomic ratio in the novel metal alloy is generally at least about4:1 (i.e., weight ratio of about 3:1). In yet another and/or alternativenon-limiting formulation, the carbon to oxygen atomic ratio in the novelmetal alloy is generally at least about 5:1 (i.e., weight ratio of about3.75:1). In still yet another and/or alternative non-limitingformulation, the carbon to oxygen atomic ratio in the novel metal alloyis generally about 2.5-50:1 (i.e., weight ratio of about 1.88-37.54:1).In a further and/or alternative non-limiting formulation, the carbon tooxygen atomic ratio in the novel metal alloy is generally about 2.5-20:1(i.e., weight ratio of about 1.88-15:1). In still a further and/oralternative non-limiting formulation, the carbon to oxygen atomic ratioin the novel metal alloy is generally about 2.5-10:1 (i.e., weight ratioof about 1.88-7.5:1). In yet a further and/or alternative non-limitingformulation, the carbon to oxygen atomic ratio in the novel metal alloyis generally about 2.5-5:1 (i.e., weight ratio of about 1.88-3.75:1). Ascan be appreciated, other atomic ratios of the carbon to oxygen in thenovel metal alloy can be used.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the novel metal alloy includes a controlled amount ofnitrogen. Large amounts of nitrogen in the novel metal alloy canadversely affect the ductility of the novel metal alloy. This can inturn adversely affect the elongation properties of the novel metalalloy. A nitrogen content in the novel metal alloy of over 20 ppm canbegin to cause the ductility of the novel metal alloy to unacceptablydecrease, thus adversely affect one or more physical properties of themetal alloy that are useful or desired in forming and/or using themedical device. In one non-limiting embodiment of the invention, thenovel metal alloy includes less than about 30 ppm nitrogen. In onenon-limiting formulation, the novel metal alloy includes less than about25 ppm nitrogen. In still another and/or alternative non-limitingformulation, the novel metal alloy includes less than about 10 ppmnitrogen. In yet another and/or alternative non-limiting formulation,the novel metal alloy includes less than about 5 ppm nitrogen. As can beappreciated, other amounts of nitrogen in the novel metal alloy canexist.

In a further and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy has several physical properties thatpositively affect the medical device when at least partially formed ofthe novel metal alloy. In one non-limiting embodiment of the invention,the average hardness of the novel metal alloy tube used to form themedical device is generally at least about 60 (HRC) at 77° F. In onenon-limiting aspect of this embodiment, the average hardness of thenovel metal alloy tube used to form the medical device is generally atleast about 70 (HRC) at 77° F., and typically about 80-100 (HRC) at 77°F. In another and/or alternative non-limiting embodiment of theinvention, the average ultimate tensile strength of the novel metalalloy used to form the medical device is generally at least about 60 UTS(ksi). In non-limiting aspect of this embodiment, the average ultimatetensile strength of the novel metal alloy used to form the medicaldevice is generally at least about 70 UTS (ksi), typically about 80-150UTS (ksi), and more typically about 100-150 UTS (ksi). In still anotherand/or alternative non-limiting embodiment of the invention, the averageyield strength of the novel metal alloy used to form the medical deviceis at least about 70 ksi. In one non-limiting aspect of this embodiment,the average yield strength of the novel metal alloy used to form themedical device is at least about 80 ksi, and typically about 100-140(ksi). In yet another and/or alternative non-limiting embodiment of theinvention, the average grain size of the novel metal alloy used to formthe medical device is greater than 5 ASTM (e.g., ASTM E 112-96). Thesmall grain size of the novel metal alloy enables the medical device tohave the desired elongation and ductility properties that are useful inenabling the medical device to be formed, crimped and/or expanded. Inone non-limiting aspect of this embodiment, the average grain size ofthe novel metal alloy used to form the medical device is about 5.2-10ASTM, typically, about 5.5-9 ASTM, more typically about 6-9 ASTM, stillmore typically about 6-8 ASTM, even more typically, about 6-7 ASTM, andstill even more typically about 6.5-7 ASTM. In still yet another and/oralternative non-limiting embodiment of the invention, the averagetensile elongation of the novel metal alloy used to form the medicaldevice is at least about 25%. An average tensile elongation of at least25% for the novel metal alloy is important to enable the medical deviceto be properly expanded when positioned in the treatment area of a bodypassageway. A medical device that does not have an average tensileelongation of at least about 25% can form micro-cracks and/or breakduring the forming, crimping and/or expansion of the medical device. Inone non-limiting aspect of this embodiment, the average tensileelongation of the novel metal alloy used to form the medical device isabout 25-35%. The unique combination of the rhenium content in the novelmetal alloy in combination with achieving the desired purity andcomposition of the alloy and the desired grain size of the novel metalalloy results in 1) a medical device having the desired high ductilityat about room temperature, 2) a medical device having the desired amountof tensile elongation, 3) a homogeneous or solid solution of a metalalloy having high radiopacity, 4) a reduction or prevention ofmicrocrack formation and/or breaking of the metal alloy tube when themetal alloy tube is sized and/or cut to form the medical device, 5) areduction or prevention of microcrack formation and/or breaking of themedical device when the medical device is crimped onto a balloon and/orother type of medical device for insertion into a body passageway, 6) areduction or prevention of microcrack formation and/or breaking of themedical device when the medical device is bent and/or expanded in a bodypassageway, 7) a medical device having the desired ultimate tensilestrength and yield strength, 8) a medical device that can have very thinwall thicknesses and still have the desired radial forces needed toretain the body passageway on an open state when the medical device hasbeen expanded, and/or 9) a medical device that exhibits less recoil whenthe medical device is crimped onto a delivery system and/or expanded ina body passageway.

Several non-limiting examples of the novel metal alloy in accordancewith the present invention are set forth below:

Metal/Wt. % Ex. 1 Ex. 2 Ex. 3 C ≦150 ppm ≦150 ppm ≦150 ppm Mo 50-60%50-60% 50-55% O ≦100 ppm ≦100 ppm ≦100 ppm N ≦40 ppm ≦40 ppm ≦40 ppm Re40-50% 40-50% 45-50% Ti ≦0.5% ≦0.5% ≦0.5% Y ≦0.1% ≦0.1% ≦0.1% Zr ≦0.25%≦0.25% ≦0.25% Metal/Wt. % Ex. 4 Ex. 5 Ex. 6 C ≦150 ppm ≦150 ppm ≦150 ppmCa 0% 0% 0% Mg 0% 0% 0% Mo 50-60% 50-60% 50-55% O ≦100 ppm ≦100 ppm ≦100ppm N ≦40 ppm ≦40 ppm ≦40 ppm Nb 0% ≦5% 0% Rare Earth Metal 0% ≦4% 0% Re40-50% 40-50% 45-50% Ta 0% ≦3% 0% Ti 0% ≦1% 0% W 0% ≦3% 0% Y 0% ≦0.1% 0%Zn 0% ≦0.1% 0% Zr 0% ≦2% 0% Metal/Wt. % Ex. 7 Ex. 8 Ex. 9 C ≦150 ppm≦150 ppm ≦150 ppm Ca 0% 0% 0% Mg 0% 0% 0% Mo 52-55.5% 51-58% 50-56% O≦100 ppm ≦100 ppm ≦100 ppm N ≦20 ppm ≦20 ppm ≦20 ppm Rare Earth Metal 0%0% 0% Re 44.5-48% 42-49% 44-50% Ta 0% 0% 0% Ti 0% 0% 0% W 0% 0% 0% Y 0%0% 0% Zn 0% 0% 0% Zr 0% 0% 0%

In examples 1-9 above, the novel metal alloy is principally formed ofrhenium and molybdenum. The novel metal alloy may also includecontrolled amounts of titanium, yttrium and/or zirconium. The content ofother metals and/or impurities is less than about 0.2 weight percent ofthe novel metal alloy. In the examples above, the ratio of carbon tooxygen is at least about 2.5:1 (i.e., weight ratio of carbon to oxygenof at least about 1.88:1), and the average grain size of novel metalalloy is about 6-10 ASTM.

Additional non-limiting examples of the novel metal alloy in accordancewith the present invention are set forth below:

Metal/Wt. % Ex. 10 Ex. 11 Ex. 12 C <150 ppm <50 ppm <50 ppm Mo 51-54%52.5-55.5% 50.5-52.4% O <50 ppm <10 ppm <10 ppm N <20 ppm <10 ppm <10ppm Re 46-49% 44.5-47.5% 47.6-49.5% Metal/Wt. % Ex. 13 Ex. 14 Ex. 15 Ex.16 C ≦50 ppm ≦50 ppm ≦50 ppm ≦50 ppm Mo 51-54% 52.5-55.5% 52-56%52.5-55% O ≦20 ppm ≦20 ppm ≦10 ppm ≦10 ppm N ≦20 ppm ≦20 ppm ≦10 ppm ≦10ppm Re 46-49% 44.5-47.5% 44-48% 45-47.5% Ti ≦0.4% ≦0.4% 0.2-0.4%0.3-0.4% Y ≦0.1% ≦0.1% 0-0.08% 0.005-0.05% Zr ≦0.2% ≦0.2% 0-0.2%0.1-0.25% Metal/Wt. % Ex. 17 Ex. 18 Ex. 19 Ex. 20 C ≦40 ppm ≦40 ppm ≦40ppm ≦40 ppm Mo 50.5-53% 51.5-54% 52-55% 52.5-55% O ≦15 ppm ≦15 ppm ≦15ppm ≦10 ppm N ≦10 ppm ≦10 ppm ≦10 ppm ≦10 ppm Re 47-49.5% 46-48.5%45-48% 45-47.5% Ti 0.1-0.35% 0% 0% 0.1-0.3% Y 0% 0.002-0.08% 0% 0% Zr 0%0% 00.1-0.2% 0.05-0.15% Metal/Wt. % Ex. 21 Ex. 22 C ≦40 ppm ≦40 ppm Mo52-55% 52.5-55.5% O ≦10 ppm ≦10 ppm N ≦10 ppm ≦10 ppm Re 45-49%44.5-47.5% Ti 0.05-0.4% 0% Y 0.005-0.07% 0.004-0.06% Zr 0% 0.1-0.2%

In examples 10-12 above, the novel metal alloy is principally formed ofrhenium and molybdenum and the content of other metals and/or impuritiesis less than about 0.1 weight percent of the novel metal alloy, theatomic ratio of carbon to oxygen is about 2.5-10:1 (i.e., weight ratioof about 1.88-7.5:1), the average grain size of the novel metal alloy isabout 6-9 ASTM, the tensile elongation of the metal alloy is about25-35%, the average density of the metal alloy is at least about 13.4gm/cc, the average yield strength of the metal alloy is about 98-122(ksi), the average ultimate tensile strength of the metal alloy is about100-150 UTS (ksi), and the average hardness of the metal alloy is about80-100 (HRC) at 77° F. In examples 13-22 above, the novel metal alloy isprincipally formed of rhenium and molybdenum and at least one metal oftitanium, yttrium and/or zirconium, and the content of other metalsand/or impurities is less than about 0.1 weight percent of the novelmetal alloy, the ratio of carbon to oxygen is about 2.5-10:1, theaverage grain size of the novel metal alloy is about 6-9 ASTM, thetensile elongation of the metal alloy is about 25-35%, the averagedensity of the metal alloy is at least about 13.6 gm/cc, the averageyield strength of the metal alloy is at least about 110 (ksi), theaverage ultimate tensile strength of the metal alloy is about 100-150UTS (ksi), and the average hardness of the metal alloy is about 80-100(HRC) at 77° F.

In another and/or alternative non-limiting aspect of the presentinvention, the use of the novel metal alloy in the medical device canincrease the strength of the medical device as compared with stainlesssteel or chromium-cobalt alloys, thus less quantity of novel metal alloycan be used in the medical device to achieve similar strengths ascompared to medical devices formed of different metals. As such, theresulting medical device can be made smaller and less bulky by use ofthe novel metal alloy without sacrificing the strength and durability ofthe medical device. Such a medical device can have a smaller profile,thus can be inserted in smaller areas, openings and/or passageways. Thenovel metal alloy also can increase the radial strength of the medicaldevice. For instance, the thickness of the walls of the medical deviceand/or the wires used to form the medical device can be made thinner andachieve a similar or improved radial strength as compared with thickerwalled medical devices formed of stainless steel or cobalt and chromiumalloy. The novel metal alloy also can improve stress-strain properties,bendability and flexibility of the medical device, thus increase thelife of the medical device. For instance, the medical device can be usedin regions that subject the medical device to bending. Due to theimproved physical properties of the medical device from the novel metalalloy, the medical device has improved resistance to fracturing in suchfrequent bending environments. In addition or alternatively, theimproved bendability and flexibility of the medical device due to theuse of the novel metal alloy can enable the medical device to be moreeasily inserted into a body passageway. The novel metal alloy can alsoreduce the degree of recoil during the crimping and/or expansion of themedical device. For example, the medical device better maintains itscrimped form and/or better maintains its expanded form after expansiondue to the use of the novel metal alloy. As such, when the medicaldevice is to be mounted onto a delivery device when the medical deviceis crimped, the medical device better maintains its smaller profileduring the insertion of the medical device in a body passageway. Also,the medical device better maintains its expanded profile after expansionso as to facilitate in the success of the medical device in thetreatment area. In addition to the improved physical properties of themedical device by use of the novel metal alloy, the novel metal alloyhas improved radiopaque properties as compared to standard materialssuch as stainless steel or cobalt-chromium alloy, thus reducing oreliminating the need for using marker materials on the medical device.For instance, the novel metal alloy is at least about 10-20% moreradiopaque than stainless steel or cobalt-chromium alloy. Specifically,the novel metal alloy can be at least about 33% more radiopaque thancobalt-chromium alloy and at least about 41.5% more radiopaque thanstainless steel.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the medical device that is at least partially formedfrom the novel metal alloy can be formed by a variety of manufacturingtechniques. In one non-limiting embodiment of the invention, the medicaldevice can be formed from a rod or tube of the novel metal alloy. If asolid rod of the novel metal alloy is formed, the rod can be drilled(e.g., gun drilled, EDM, etc.) to form a cavity or passageway partiallyor fully through the rod. The rod or tube can be cleaned, polished,annealed, drawn, etc. to obtain the desired diameter and/or wallthickness of the metal tube. After the metal tube has been formed to thedesired diameter and wall thickness, the metal tube can be formed into amedical device by a process such as, but not limited to, laser cutting,etching, etc. After the medical device has been formed, the medicaldevice can be cleaned, polished, sterilized, etc. for final processingof the medical device. As can be appreciated, other or additionalprocess steps can be used to at least partially form the medical devicefrom the novel metal alloy.

In a further and/or alternative non-limiting aspect of the presentinvention, the novel alloy used to at least partially form the medicaldevice is initially formed into a rod or a tube of novel metal alloy.The novel metal alloy rod or tube can be formed by various techniquessuch as, but not limited to, 1) melting the novel metal alloy and/ormetals that form the novel metal alloy (e.g., vacuum arc melting, etc.)and then extruding and/or casting the novel metal alloy into a rod ortube, 2) melting the novel metal alloy and/or metals that form the novelmetal alloy, forming a metal strip and then rolling and welding thestrip into a tube, or 3) consolidating metal power of the novel metalalloy and/or metal powder of metals that form the novel metal alloy. Inone non-limiting process, the rod or tube of the novel metal alloy isformed by consolidating metal power. In this process, fine particles ofmolybdenum and rhenium along with any additives are mixed to form ahomogenous blend of particles. Typically, the average particle size ofthe metal powders is less than about 200 mesh (e.g., less than 74microns). A larger average particle size can interfere with the propermixing of the metal powders and/or adversely affect one or more physicalproperties of the rod or tube formed from the metal powders. In onenon-limiting embodiment, the average particle size of the metal powdersis less than about 230 mesh (e.g., less than 63 microns). In anotherand/or alternative non-limiting embodiment, the average particle size ofthe metal powders is about 230-635 mesh (i.e., about 20-63 microns). Ascan be appreciated, smaller average particle sizes can be used. Thepurity of the metal powders should be selected so that the metal powderscontain very low levels of carbon, oxygen and nitrogen. Typically thecarbon content of the molybdenum metal powder is less than about 100ppm, the oxygen content of the molybdenum metal powder is less thanabout 50 ppm, and the nitrogen content of the molybdenum metal powder isless than about 20 ppm. Typically, the carbon content of the rheniummetal powder is less than about 100 ppm, the oxygen content of therhenium metal powder is less than about 50 ppm, and the nitrogen contentof the rhenium metal powder is less than about 20 ppm. Typically, metalpowder having a purity grade of at least 99.9 and more typically atleast about 99.95 should be used to obtain the desired purity of thepowders of molybdenum and rhenium. When titanium, yttrium and/orzirconium powder is added to the metal powder mixture, the amount ofcarbon, oxygen and nitrogen in the power should also be minimized.Typically, metal powder having a purity grade of at least 99.8 and moretypically at least about 99.9 should be used to obtain the desiredpurity of the powders of titanium, yttrium and/or zirconium. The blendof metal powder is then pressed together to form a solid solution of thenovel metal alloy into a rod or tube. Typically, the pressing process isby an isostatic process (i.e., uniform pressure applied from all sideson the metal powder). When the metal powders are pressed togetherisostatically, cold isostatic pressing (CIP) is typically used toconsolidate the metal powders; however, this is not required. Thepressing process can be preformed in an inert atmosphere, an oxygenreducing atmosphere (e.g., hydrogen, argon and hydrogen mixture, etc.)and/or under a vacuum; however, this is not required. The averagedensity of the rod or tube that is achieved by pressing together themetal powders is about 80-90% of the final average density of the rod ortube or about 70-95% the minimum theoretical density of the novel metalalloy. After the metal powders are pressed together, the pressed metalpowders are sintered at high temperature (e.g., 2000-2500° C.) to fusethe metal powders together to form the solid metal rod or tube. Thesintering of the consolidated metal powder can be preformed in an oxygenreducing atmosphere (e.g., hydrogen, argon and hydrogen mixture, etc.)and/or under a vacuum; however, this is not required. At the highsintering temperatures, a high hydrogen atmosphere will reduce both theamount of carbon and oxygen in the formed rod or tube. The sinteredmetal powder generally has an as-sintered average density of about90-99% the minimum theoretical density of the novel metal alloy.Typically, the sintered rod or tube has a final average density of atleast about 12 gm/cc, typically at least about 12.5 gm/cc, and moretypically about 13-14 gm/cc. Typically, the rod or tube is formed tohave a length of about 48 inches or less; however, longer lengths can beformed. A rod or tube formed by this process typically has an averageconcentricity deviation that is less than a rod or tube formed by an arcmelting and molding process and a sheet and welding process. Generally,the average concentricity deviation of the rod or tube that is formedfrom compressed and sintered metal powders is less than about 20%,typically about 1-18%, and more typically about 1-5%. The average outerdiameter of the rod or tube is typically less than about 2 inches, moretypically less than about 1 inch, and even more typically no more thanabout 0.5 inch; however, larger tube sizes can be formed. In onenon-limiting tube configuration, the tube has an inner diameter of about0.31 inch plus or minus about 0.002 inch and an outer diameter of about0.5 inch plus or minus about 0.002 inch. The wall thickness of the tubeis about 0.095 inch plus or minus about 0.002 inch. As can beappreciated, this is just one example of many different sized tubes thatcan be formed.

In still a further and/or alternative non-limiting aspect of the presentinvention, when a solid rod of the novel metal alloy is formed, the rodis then formed into a tube prior to reducing the diameter of the rod.The rod can be formed into a tube by a variety of processes such as, butnot limited to, drilling (e.g., gun drilling, etc.) or by cutting (e.g.,EDM, etc.). The cavity or passageway formed in the rod typically isformed fully through the rod; however, this is not required.

In yet a further and/or alternative non-limiting aspect of the presentinvention, the rod or tube can be cleaned and/or polished after the rodor tube has been formed; however, this is not required. Typically, therod or tube is cleaned and/or polished prior to being further processed;however, this is not required. When a rod of the novel metal alloy isformed into a tube, the formed tube is typically cleaned and/or polishedprior to being further process; however, this is not required. When therod or tube is resized and/or annealed as discussed in detail below, theresized and/or annealed rod or tube is typically cleaned and/or polishedprior to and/or after each or after a series of resizing and/orannealing processes; however, this is not required. The cleaning and/orpolishing of the rod or tube is used to remove impurities and/orcontaminants from the surfaces of the rod or tube. Impurities andcontaminants can become incorporated into the novel metal alloy duringthe processing of the rod or tube. The inadvertent incorporation ofimpurities and contaminants in the rod or tube can result in anundesired amount of carbon, nitrogen and/or oxygen, and/or otherimpurities in the novel metal alloy. The inclusion of impurities andcontaminants in the novel metal alloy can result in prematuremicro-cracking of the novel metal alloy and/or an adverse affect on oneor more physical properties of the novel metal alloy (e.g., decrease intensile elongation, increased ductility, etc.). The cleaning of thenovel metal alloy can be accomplished by a variety of techniques suchas, but not limited to, 1) using a solvent (e.g., acetone, methylalcohol, etc.) and wiping the novel metal alloy with a Kimwipe or otherappropriate towel, 2) by at least partially dipping or immersing thenovel metal alloy in a solvent and then ultrasonically cleaning thenovel metal alloy, and/or 3) by at least partially dipping or immersingthe novel metal alloy in a pickling solution. As can be appreciated, thenovel metal alloy can be cleaned in other or additional ways. If thenovel metal alloy is to be polished, the novel metal alloy is generallypolished by use of a polishing solution that typically includes an acidsolution; however, this is not required. In one non-limiting example,the polishing solution includes sulfuric acid; however, other oradditional acids can be used. In one non-limiting polishing solution,the polishing solution can include by volume 60-95% sulfuric acid and5-40% de-ionized water (DI water). Typically, the polishing solutionthat includes an acid will increase in temperature during the making ofthe solution and/or during the polishing procedure. As such, thepolishing solution is typically stirred and/or cooled during making ofthe solution and/or during the polishing procedure. The temperature ofthe polishing solution is typically about 20-100° C., and typicallygreater than about 25° C. One non-limiting polishing technique that canbe used is an electro-polishing technique. When an electro-polishingtechnique is used, a voltage of about 2-30V, and typically about 5-12Vis applied to the rod or tube during the polishing process; however, itwill be appreciated that other voltages can be used. The time used topolish the novel metal alloy is dependent on both the size of the rod ortube and the amount of material that needs to be removed from the rod ortube. The rod or tube can be processed by use of a two-step polishingprocess wherein the novel metal alloy piece is at least partiallyimmersed in the polishing solution for a given period (e.g., 0.1-15minutes, etc.), rinsed (e.g., DI water, etc.) for a short period of time(e.g., 0.02-1 minute, etc.), and then flipped over and at leastpartially immersed in the solution again for the same or similarduration as the first time; however, this is not required. The novelmetal alloy can be rinsed (e.g., DI water, etc.) for a period of time(e.g., 0.01-5 minutes, etc.) before rinsing with a solvent (e.g.,acetone, methyl alcohol, etc.); however, this is not required. The novelmetal alloy can be dried (e.g., exposure to the atmosphere, maintainedin an inert gas environment, etc.) on a clean surface. These polishingprocedures can be repeated until the desired amount of polishing of therod or tube is achieved.

In still yet a further and/or alternative non-limiting aspect of thepresent invention, the rod or tube is resized to the desired dimensionof the medical device. In one non-limiting embodiment, the diameter ofthe rod or tube is reduced to a final rod or tube dimension in a singlestep or by a series of steps. During the reduction a rod or tube, theouter rod or tube diameter, the inner rod or tube diameter and/or wallthickness of the rod or tube are typically reduced; however, this is notrequired. The outer diameter size of the rod or tube is typicallyreduced by the use of one or more drawing processes. During the drawingprocess, care should be taken to not form micro-cracks in the rod ortube during the reduction of the rod or tube outer diameter. Generally,the rod or tube should not be reduced in outer diameter by more about25% each time the rod or tube is drawn through a reducing mechanism(e.g., a die, etc.). In one non-limiting process step, the rod or tubeis reduced in outer diameter by about 0.1-20% each time the rod or tubeis drawn through a reducing mechanism. In another and/or alternativenon-limiting process step, the rod or tube is reduced in outer diameterby about 1-15% each time the rod or tube is drawn through a reducingmechanism. In still another and/or alternative non-limiting processstep, the rod or tube is reduced in outer diameter by about 2-15% eachtime the rod or tube is drawn through reducing mechanism. In yet anotherone non-limiting process step, the rod or tube is reduced in outerdiameter by about 5-10% each time the rod or tube is drawn throughreducing mechanism. In another and/or alternative non-limitingembodiment of the invention, the rod or tube of novel metal alloy isdrawn through a die to reduce the outer diameter of the rod or tube. Thedrawing process is typically a cold drawing process or a plug drawingprocess through a die. When a cold drawing or mandrel drawing process isused, a lubricant (e.g., grease, etc.) is typically coated on the outersurface of the rod or tube and the rod or tube is then drawn though thedie. Typically, little or no heat is used during the cold drawingprocess. After the rod or tube has been drawn through the die, the outersurface of the rod or tube is typically cleaned with a solvent to removethe lubricant so as to limit the amount of impurities that areincorporated in the novel metal alloy. This cold drawing process can berepeated several times until the desired outer diameter, inner diameterand/or wall thickness of the rod or tube is achieved. A plug drawingprocess can also or alternatively be used to size the rod or tube. Theplug drawing process typically does not use a lubricant during thedrawing process. The plug drawing process typically includes a heatingstep to heat the rod or tube prior and/or during the drawing of the rodor tube through the die. The elimination of the use of a lubricant canreduce the incidence of impurities being introduced into the metal alloyduring the drawing process. During the plug drawing process, the rod ortube can be protected from oxygen and nitrogen by use of a vacuumenvironment, an oxygen reducing environment (e.g., hydrogen, argon andhydrogen mixture, etc.) or an inert environment. One non-limitingprotective environment includes argon, hydrogen or argon and hydrogen;however, other or additional inert gasses can be used. As indicatedabove, the rod or tube is typically cleaned after each drawing processto remove impurities and/or other undesired materials from the surfaceof the rod or tube; however, this is not required.

In still yet a further and/or alternative non-limiting aspect of thepresent invention, the rod or tube is annealed after one or more drawingprocesses. The metal alloy rod or tube can be annealed after eachdrawing process or after a plurality of drawing processes. The metalalloy rod or tube is typically annealed prior to about a 60% outerdiameter size reduction of the metal alloy rod or tube. In other words,the rod or tube should not be reduced in outer diameter by more than 60%before being annealed. A too large of a reduction in the outer diameterof the metal alloy rod or tube during the drawing process prior to therod or tube being annealed can result in micro-cracking of the rod ortube. In one non-limiting processing step, the metal alloy rod or tubeis annealed prior to about a 50% outer diameter size reduction of themetal alloy rod or tube. In another and/or alternative non-limitingprocessing step, the metal alloy rod or tube is annealed prior to abouta 45% outer diameter size reduction of the metal alloy rod or tube. Instill another and/or alternative non-limiting processing step, the metalalloy rod or tube is annealed prior to about a 1-45% outer diameter sizereduction of the metal alloy rod or tube. In yet another and/oralternative non-limiting processing step, the metal alloy rod or tube isannealed prior to about a 5-30% outer diameter size reduction of themetal alloy rod or tube. In still yet another and/or alternativenon-limiting processing step, the metal alloy rod or tube is annealedprior to about a 5-15% outer diameter size reduction of the metal alloyrod or tube. When the rod or tube is annealed, the rod or tube istypically heated to a temperature of about 1300-1700° C. for a period ofabout 2-200 minutes; however, other temperatures and/or times can beused. In one non-limiting processing step, the metal alloy rod or tubeis annealed at a temperature of about 1400-1600° C. for about 2-30minutes. The annealing process typically occurs in an inert environmentor an oxygen reducing environment so as to limit the amount ofimpurities that may embed themselves in the novel metal alloy during theannealing process. One non-limiting oxygen reducing environment that canbe used during the annealing process is a hydrogen environment; however,it can be appreciated that a vacuum environment can be used or one ormore other or additional gasses can be used to create the oxygenreducing environment. At the annealing temperatures, a hydrogencontaining atmosphere can further reduce the amount of oxygen in the rodor tube. The chamber in which the rod or tube is annealed should besubstantially free of impurities (e.g., carbon, oxygen, and/or nitrogen)so as to limit the amount of impurities that can embed themselves in therod or tube during the annealing process. The annealing chambertypically is formed of a material that will not impart impurities to therod or tube as the rod or tube is being annealed. A non-limitingmaterial that can be used to form the annealing chamber includes, but isnot limited to, molybdenum, rhenium, tungsten, molybdenum TZM alloy,ceramic, etc. When the rod or tube is restrained in the annealingchamber, the restraining apparatuses that are used to contact the novelmetal alloy rod or tube are typically formed of materials that will notintroduce impurities to the novel metal alloy during the processing ofthe rod or tube. Non-limiting examples of materials that can be used toat least partially form the restraining apparatuses include, but are notlimited to, molybdenum, titanium, yttrium, zirconium, rhenium and/ortungsten.

In another and/or alternative non-limiting aspect of the presentinvention, the rod or tube can be cleaned prior to and/or after beingannealed. The cleaning process is designed to remove impurities and/orother materials from the surfaces of the rod or tube. Impurities thatare on one or more surfaces of the rod or tube can become permanentlyembedded into the rod or tube during the annealing processes. Theseimbedded impurities can adversely affect the physical properties of thenovel metal alloy as the rod or tube is formed into a medical device,and/or can adversely affect the operation and/or life of the medicaldevice. In one non-limiting embodiment of the invention, the cleaningprocess includes a delubrication or degreasing process which istypically followed by pickling process; however, this is not required.The delubrication or degreasing process followed by pickling process aretypically used when a lubricant has been used on the rod or tube duringa drawing process. Lubricants commonly include carbon compounds andother types of compounds that can adversely affect the novel metal alloyif such compounds and/or elements in such compounds become associatedand/or embedded with the novel metal alloy during an annealing process.The delubrication or degreasing process can be accomplished by a varietyof techniques such as, but not limited to, 1) using a solvent (e.g.,acetone, methyl alcohol, etc.) and wiping the novel metal alloy with aKimwipe or other appropriate towel, and/or 2) by at least partiallydipping or immersing the novel metal alloy in a solvent and thenultrasonically cleaning the novel metal alloy. As can be appreciated,the novel metal alloy can be delubricated or degreased in other oradditional ways. After the novel metal alloy rod or tube has beendelubricated or degreased, the rod or tube can be further cleaned by useof a pickling process. The pickling process, when used, includes the useof one or more acids to remove impurities from the surface of the rod ortube. Non-limiting examples of acids that can be used as the picklingsolution include, but are not limited to, nitric acid, acetic acid,sulfuric acid, hydrochloric acid, and/or hydrofluoric acid. These acidsare typically analytical reagent (ACS) grade acids. The acid solutionand acid concentration are selected to remove oxides and otherimpurities on the rod or tube surface without damaging or over etchingthe surface of the rod or tube. A rod or tube surface that includes alarge amount of oxides typically requires a stronger pickling solutionand/or long picking process times. Non-limiting examples of picklingsolutions include 1) 25-60% DI water, 30-60% nitric acid, and 2-20%sulfuric acid; 2) 40-75% acetic acid, 10-35% nitric acid, and 1-12%hydrofluoric acid; and 3) 50-100% hydrochloric acid. As can beappreciated, one or more different pickling solutions can be used duringthe pickling process. During the pickling process, the rod or tube isfully or partially immersed in the pickling solution for a sufficientamount of time to remove the impurities from the surface of the rod ortube. Typically, the time period for pickling is about 2-120 seconds;however, other time periods can be used. After the rod or tube has beenpickled, the rod or tube is typically rinsed with a water (e.g., DIwater, etc.) and/or a solvent (e.g., acetone, methyl alcohol, etc.) toremove any pickling solution from the rod or tube and then the rod ortube is allowed to dry. The rod or tube may be keep in an protectiveenvironment during the rinse and/or drying process to inhibit or preventoxides from reforming on the surface of the rod or tube prior to the rodor tube being annealed; however, this is not required.

In yet another and/or alternative non-limiting aspect of the presentinvention, the restraining apparatuses that are used to contact thenovel metal alloy rod or tube during an annealing process and/or drawingprocess are typically formed of materials that will not introduceimpurities to the novel metal alloy during the processing of the rod ortube. In one non-limiting embodiment, when the metal alloy rod or tubeis exposed to temperatures above 150° C., the materials that contact thenovel metal alloy rod or tube during the processing of the rod or tubeare typically made from molybdenum, rhenium and/or tungsten. When thenovel metal alloy rod or tube is processed at lower temperatures (i.e.,150° C. or less), materials made from Teflon parts can also oralternatively be used.

In still another and/or alternative non-limiting aspect of the presentinvention, the novel metal alloy rod or tube, after being formed to thedesired outer diameter, inner diameter and/or wall thickness, can be cutand/or etched to at least partially form the desired configuration ofthe medical device (e.g., stent, etc.). In one non limiting embodimentof the invention, the novel metal alloy rod or tube is at leastpartially cut by a laser. The laser is typically desired to have a beamstrength which can heat the novel metal alloy rod or tube to atemperature of at least about 2200-2300° C. In one non-limiting aspectof this embodiment, a pulsed YAGI-ND or CO₂ laser is used to at leastpartially cut a pattern of medical device out of the novel metal alloyrod or tube. In another and/or alternative non-limiting aspect of thisembodiment, the cutting of the novel metal alloy rod or tube by thelaser can occurs in a vacuum environment, an oxygen reducingenvironment, or an inert environment; however, this is not required. Ithas been found that laser cutting of the rod or tube in a non-protectedenvironment can result in impurities being introduced into the cut rodor tube, which introduced impurities can induce micro-cracking of therod or tube during the cutting of the rod or tube. One non-limitingoxygen reducing environment includes a combination of argon andhydrogen; however, a vacuum environment, an inert environment, or otheror additional gasses can be used to form the oxygen reducingenvironment. In still another and/or alternative non-limiting aspect ofthis embodiment, the novel metal alloy rod or tube is stabilized so asto limit or prevent vibration of the rod or tube during the cuttingprocess. The apparatus used to stabilize the rod or tube can be formedof molybdenum, rhenium, tungsten, molybdenum TZM alloy, ceramic, etc. soas to not introduce contaminants to the rod or tube during the cuttingprocess; however, this is not required. Vibrations in the rod or tubeduring the cutting of the rod or tube can result in the formation ofmicro-cracks in the rod or tube as the rod or tube is cut. The averageamplitude of vibration during the cutting of the rod or tube should beno more than about 150% the wall thickness of the rod or tube. In onenon-limiting aspect of this embodiment, the average amplitude ofvibration should be no more than about 100% the wall thickness of therod or tube. In another non-limiting aspect of this embodiment, theaverage amplitude of vibration should be no more than about 75% the wallthickness of the rod or tube. In still another non-limiting aspect ofthis embodiment, the average amplitude of vibration should be no morethan about 50% the wall thickness of the rod or tube. In yet anothernon-limiting aspect of this embodiment, the average amplitude ofvibration should be no more than about 25% the wall thickness of the rodor tube. In still yet another non-limiting aspect of this embodiment,the average amplitude of vibration should be no more than about 15% thewall thickness of the rod or tube.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the novel metal alloy rod or tube, after being formedto the desired medical device, can be cleaned, polished, sterilized,etc. for final processing of the medical device. In one non-limitingembodiment of the invention, the medical device is electropolished. Inone non-limiting aspect of this embodiment, the medical device iscleaned prior to being exposed to the polishing solution; however, thisis not required. The cleaning process, when used, can be accomplished bya variety of techniques such as, but not limited to, 1) using a solvent(e.g., acetone, methyl alcohol, etc.) and wiping the medical device witha Kimwipe or other appropriate towel, and/or 2) by at least partiallydipping or immersing the medical device in a solvent and thenultrasonically cleaning the medical device. As can be appreciated, themedical device can be cleaned in other or additional ways. In anotherand/or alternative non-limiting aspect of this embodiment, the polishingsolution can include one or more acids. One non-limiting formulation ofthe polishing solution includes about 10-80 percent by volume sulfuricacid. As can be appreciated, other polishing solution compositions canbe used. In still another and/or alternative non-limiting aspect of thisembodiment, about 5-12 volts are directed to the medical device duringthe electropolishing process; however, other voltage levels can be used.In yet another and/or alternative non-limiting aspect of thisembodiment, the medical device is rinsed with water and/or a solvent andallowed to dry to remove polishing solution on the medical device.

In one non-limiting process for manufacturing a medical device inaccordance with the present invention, the process includes thefollowing process steps: 1) forming a novel metal alloy rod or tube; 2)resizing the rod or tube, 3) cleaning and/or pickling the surface of therod or tube prior to annealing the rod or tube; 4) annealing the rod ortube; and 5) repeating steps 2-4 until the rod or tube has been sized tothe desired size. In another and/or alternative non-limiting process formanufacturing a medical device in accordance with the present invention,the process includes the following process steps: 1) forming a novelmetal alloy rod or tube; 2) resizing the rod or tube by use of a mandreland/or plug drawing process, 3) cleaning and/or pickling the surface ofthe rod or tube prior to annealing the rod or tube; 4) annealing the rodor tube prior to a 60% outer diameter size reduction of the rod or tube;5) repeating steps 2-4 until the rod or tube has been sized to thedesired size; 6) cutting and/or etching the rod or tube to at leastpartially form the medical device; and 7) cleaning and/orelectropolishing the medical device. In still another and/or alternativenon-limiting process for manufacturing a medical device in accordancewith the present invention, the process includes the following processsteps: 1) consolidating metal power of the novel metal alloy and/ormetal powder of metals that form the novel metal alloy into a tube; 2)resizing the tube one or more times by use of a plug drawing process, 3)cleaning and/or pickling the surface of the tube after each plug drawingprocess; 4) annealing the tube prior to a 45% outer diameter sizereduction of the tube; 5) repeating steps 2-4 until the tube has beensized to the desired size; 6) laser cutting the tube to at leastpartially form the medical device; and 7) cleaning and/orelectropolishing the medical device. As can be appreciated, other oradditional process steps can be used to form the medical device from anovel metal alloy. In each of the non-limiting processes set forthabove, the medical device can be further processed to include 1) amarker material, 2) one or more biological agents, 3) one or morepolymer coatings, and/or 4) one or more surface or microstructures.

In yet another and/or alternative non-limiting aspect of the presentinvention, the medical device can include, contain and/or be coated withone or more biological agents that facilitate in the success of themedical device and/or treated area. The medical device can include,contain and/or be coated with one or more biological agents that inhibitor prevent in-stent restenosis, vascular narrowing, and/or thrombosisduring and/or after the medical device is inserted into a treatmentarea; however, this is not required. In addition or alternatively, themedical device can include, contain and/or be coated with one or morebiological agents that can be used in conjunction with the one or morebiological agents that inhibit or prevent in-stent restenosis, vascularnarrowing, and/or thrombosis that are included in, contained in and/orcoated in the medical device. As such, the medical device, when itincludes, contains, and/or is coated with one or more biological agents,can include one or more biological agents to address one or more medicalneeds. The term “biological agent” includes, but is not limited to, asubstance, drug, or otherwise formulated and/or designed to prevent,inhibit and/or treat one or more biological problems, and/or to promotethe healing in a treated area. Non-limiting examples of biologicalproblems that can be addressed by one or more biological agents include,but are not limited to, viral, fungus and/or bacteria infection;vascular diseases and/or disorders; digestive diseases and/or disorders;reproductive diseases and/or disorders; lymphatic diseases and/ordisorders; cancer; implant rejection; pain; nausea; swelling; arthritis;bone diseases and/or disorders; organ failure; immunity diseases and/ordisorders; cholesterol problems; blood diseases and/or disorders; lungdiseases and/or disorders; heart diseases and/or disorders; braindiseases and/or disorders; neuralgia diseases and/or disorders; kidneydiseases and/or disorders; ulcers; liver diseases and/or disorders;intestinal diseases and/or disorders; gallbladder diseases and/ordisorders; pancreatic diseases and/or disorders; psychologicaldisorders; respiratory diseases and/or disorders; gland diseases and/ordisorders; skin diseases and/or disorders; hearing diseases and/ordisorders; oral diseases and/or disorders; nasal diseases and/ordisorders; eye diseases and/or disorders; fatigue; genetic diseasesand/or disorders; burns; scarring and/or scars; trauma; weight diseasesand/or disorders; addiction diseases and/or disorders; hair loss;cramps; muscle spasms; tissue repair; and/or the like. Non-limitingexamples of biological agents that can be used include, but are notlimited to, 5-Fluorouracil and/or derivatives thereof;5-Phenylmethimazole and/or derivatives thereof; ACE inhibitors and/orderivatives thereof; acenocoumarol and/or derivatives thereof; acyclovirand/or derivatives thereof; actilyse and/or derivatives thereof;adrenocorticotropic hormone and/or derivatives thereof; adriamycinand/or derivatives thereof; agents that modulate intracellular Ca₂₊transport such as L-type (e.g., diltiazem, nifedipine, verapamil, etc.)or T-type Ca₂₊ channel blockers (e.g., amiloride, etc.);alpha-adrenergic blocking agents and/or derivatives thereof; alteplaseand/or derivatives thereof; amino glycosides and/or derivatives thereof(e.g., gentamycin, tobramycin, etc.); angiopeptin and/or derivativesthereof; angiostatic steroid and/or derivatives thereof; angiotensin IIreceptor antagonists and/or derivatives thereof; anistreplase and/orderivatives thereof; antagonists of vascular epithelial growth factorand/or derivatives thereof; anti-biotics; anti-coagulant compoundsand/or derivatives thereof; anti-fibrosis compounds and/or derivativesthereof; anti-fungal compounds and/or derivatives thereof;anti-inflammatory compounds and/or derivatives thereof; Anti-InvasiveFactor and/or derivatives thereof; anti-metabolite compounds and/orderivatives thereof (e.g., staurosporin, trichothecenes, and modifieddiphtheria and ricin toxins, Pseudomonas exotoxin, etc.); anti-matrixcompounds and/or derivatives thereof (e.g., colchicine, tamoxifen,etc.); anti-microbial agents and/or derivatives thereof; anti-migratoryagents and/or derivatives thereof (e.g., caffeic acid derivatives,nilvadipine, etc.); anti-mitotic compounds and/or derivatives thereof;anti-neoplastic compounds and/or derivatives thereof; anti-oxidantsand/or derivatives thereof; anti-platelet compounds and/or derivativesthereof; anti-proliferative and/or derivatives thereof;anti-thrombogenic agents and/or derivatives thereof; argatroban and/orderivatives thereof; ap-1 inhibitors and/or derivatives thereof (e.g.,for tyrosine kinase, protein kinase C, myosin light chain kinase,Ca₂₊/calmodulin kinase II, casein kinase II, etc.); aspirin and/orderivatives thereof; azathioprine and/or derivatives thereof;β-Estradiol and/or derivatives thereof; β-1-anticollagenase and/orderivatives thereof; calcium channel blockers and/or derivativesthereof; calmodulin antagonists and/or derivatives thereof (e.g., H₇,etc.); CAPTOPRIL and/or derivatives thereof; cartilage-derived inhibitorand/or derivatives thereof; ChIMP-3 and/or derivatives thereof;cephalosporin and/or derivatives thereof (e.g., cefadroxil, cefazolin,cefaclor, etc.); chloroquine and/or derivatives thereof;chemotherapeutic compounds and/or derivatives thereof (e.g.,5-fluorouracil, vincristine, vinblastine, cisplatin, doxyrubicin,adriamycin, tamocifen, etc.); chymostatin and/or derivatives thereof;CILAZAPRIL and/or derivatives thereof; clopidigrel and/or derivativesthereof; clotrimazole and/or derivatives thereof; colchicine and/orderivatives thereof; cortisone and/or derivatives thereof; coumadinand/or derivatives thereof; curacin-A and/or derivatives thereof;cyclosporine and/or derivatives thereof; cytochalasin and/or derivativesthereof (e.g., cytochalasin A, cytochalasin B, cytochalasin C,cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin G,cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin L,cytochalasin M, cytochalasin N, cytochalasin O, cytochalasin P,cytochalasin Q, cytochalasin R, cytochalasin S, chaetoglobosin A,chaetoglobosin B, chaetoglobosin C, chaetoglobosin D, chaetoglobosin E,chaetoglobosin F, chaetoglobosin G, chaetoglobosin J, chaetoglobosin K,deoxaphomin, proxiphomin, protophomin, zygosporin D, zygosporin E,zygosporin F, zygosporin G, aspochalasin B, aspochalasin C, aspochalasinD, etc.); cytokines and/or derivatives thereof; desirudin and/orderivatives thereof; dexamethazone and/or derivatives thereof;dipyridamole and/or derivatives thereof; eminase and/or derivativesthereof; endothelin and/or derivatives thereof; endothelial growthfactor and/or derivatives thereof; epidermal growth factor and/orderivatives thereof; epothilone and/or derivatives thereof; estramustineand/or derivatives thereof; estrogen and/or derivatives thereof;fenoprofen and/or derivatives thereof; fluorouracil and/or derivativesthereof; flucytosine and/or derivatives thereof; forskolin and/orderivatives thereof; ganciclovir and/or derivatives thereof;glucocorticoids and/or derivatives thereof (e.g., dexamethasone,betamethasone, etc.); glycoprotein IIb/IIIa platelet membrane receptorantibody and/or derivatives thereof; GM-CSF and/or derivatives thereof;griseofulvin and/or derivatives thereof; growth factors and/orderivatives thereof (e.g., VEGF; TGF; IGF; PDGF; FGF, etc.); growthhormone and/or derivatives thereof; heparin and/or derivatives thereof;hirudin and/or derivatives thereof; hyaluronate and/or derivativesthereof; hydrocortisone and/or derivatives thereof; ibuprofen and/orderivatives thereof; immunosuppressive agents and/or derivatives thereof(e.g., adrenocorticosteroids, cyclosporine, etc.); indomethacin and/orderivatives thereof; inhibitors of the sodium/calcium antiporter and/orderivatives thereof (e.g., amiloride, etc.); inhibitors of the IP₃receptor and/or derivatives thereof; inhibitors of the sodium/hydrogenantiporter and/or derivatives thereof (e.g., amiloride and derivativesthereof, etc.); insulin and/or derivatives thereof; Interferon alpha 2Macroglobulin and/or derivatives thereof; ketoconazole and/orderivatives thereof; Lepirudin and/or derivatives thereof; LISINOPRILand/or derivatives thereof; LOVASTATIN and/or derivatives thereof;marevan and/or derivatives thereof; mefloquine and/or derivativesthereof; metalloproteinase inhibitors and/or derivatives thereof;methotrexate and/or derivatives thereof; metronidazole and/orderivatives thereof; miconazole and/or derivatives thereof; monoclonalantibodies and/or derivatives thereof; mutamycin and/or derivativesthereof; naproxen and/or derivatives thereof; nitric oxide and/orderivatives thereof; nitroprusside and/or derivatives thereof; nucleicacid analogues and/or derivatives thereof (e.g., peptide nucleic acids,etc.); nystatin and/or derivatives thereof; oligonucleotides and/orderivatives thereof; paclitaxel and/or derivatives thereof; penicillinand/or derivatives thereof; pentamidine isethionate and/or derivativesthereof; phenindione and/or derivatives thereof; phenylbutazone and/orderivatives thereof; phosphodiesterase inhibitors and/or derivativesthereof; Plasminogen Activator Inhibitor-1 and/or derivatives thereof;Plasminogen Activator Inhibitor-2 and/or derivatives thereof; PlateletFactor 4 and/or derivatives thereof; platelet derived growth factorand/or derivatives thereof; plavix and/or derivatives thereof; POSTMI 75and/or derivatives thereof; prednisone and/or derivatives thereof;prednisolone and/or derivatives thereof; probucol and/or derivativesthereof; progesterone and/or derivatives thereof; prostacyclin and/orderivatives thereof; prostaglandin inhibitors and/or derivativesthereof; protamine and/or derivatives thereof; protease and/orderivatives thereof; protein kinase inhibitors and/or derivativesthereof (e.g., staurosporin, etc.); quinine and/or derivatives thereof;radioactive agents and/or derivatives thereof (e.g., Cu-64, Ca-67,Cs-131, Ga-68, Zr-89, Ku-97, Tc-99m, Rh-105, Pd-103, Pd-109, In-111,I-123, I-125, I-131, Re-186, Re-188, Au-198, Au-199, Pb-203, At-211,Pb-212, Bi-212, H₃P³²O₄, etc.); rapamycin and/or derivatives thereof;receptor antagonists for histamine and/or derivatives thereof; refludanand/or derivatives thereof; retinoic acids and/or derivatives thereof;revasc and/or derivatives thereof; rifamycin and/or derivatives thereof;sense or anti-sense oligonucleotides and/or derivatives thereof (e.g.,DNA, RNA, plasmid DNA, plasmid RNA, etc.); seramin and/or derivativesthereof; steroids; seramin and/or derivatives thereof; serotonin and/orderivatives thereof; serotonin blockers and/or derivatives thereof;streptokinase and/or derivatives thereof; sulfasalazine and/orderivatives thereof; sulfonamides and/or derivatives thereof (e.g.,sulfamethoxazole, etc.); sulphated chitin derivatives; SulphatedPolysaccharide Peptidoglycan Complex and/or derivatives thereof; T_(H1)and/or derivatives thereof (e.g., Interleukins-2, -12, and -15, gammainterferon, etc.); thioprotese inhibitors and/or derivatives thereof;taxol and/or derivatives thereof (e.g., taxotere, baccatin,10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, cephalomannine,10-deacetyl-7-epitaxol, 7 epitaxol, 10-deacetylbaccatin III,10-deacetylcephaolmannine, etc.); ticlid and/or derivatives thereof;ticlopidine and/or derivatives thereof; tick anti-coagulant peptideand/or derivatives thereof; thioprotese inhibitors and/or derivativesthereof; thyroid hormone and/or derivatives thereof; Tissue Inhibitor ofMetalloproteinase-1 and/or derivatives thereof; Tissue Inhibitor ofMetalloproteinase-2 and/or derivatives thereof; tissue plasmaactivators; TNF and/or derivatives thereof, tocopherol and/orderivatives thereof; toxins and/or derivatives thereof; tranilast and/orderivatives thereof; transforming growth factors alpha and beta and/orderivatives thereof; trapidil and/or derivatives thereof;triazolopyrimidine and/or derivatives thereof; vapiprost and/orderivatives thereof; vinblastine and/or derivatives thereof; vincristineand/or derivatives thereof; zidovudine and/or derivatives thereof. Ascan be appreciated, the biological agent can include one or morederivatives of the above listed compounds and/or other compounds. In onenon-limiting embodiment, the biological agent includes, but is notlimited to, trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. The type and/or amount of biological agentincluded on, in and/or in conjunction with the medical device isgenerally selected for the treatment of one or more medical treatments.Typically the amount of biological agent included on, in and/or used inconjunction with the medical device is about 0.01-100 ug per mm²;however, other amounts can be used. The amount of two of more biologicalagents on, in and/or used in conjunction with the medical device can bethe same or different. In one non-limiting example, the medical devicecan be coated with and/or includes one or more biological agents suchas, but not limited to, trapidil and/or trapidil derivatives, taxol,taxol derivatives (e.g., taxotere, baccatin, 10-deacetyltaxol,7-xylosyl-10-deacetyltaxol, cephalomannine, 10-deacetyl-7-epitaxol, 7epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaolmannine, etc.),cytochalasin, cytochalasin derivatives (e.g., cytochalasin A,cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E,cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J,cytochalasin K, cytochalasin L, cytochalasin M, cytochalasin N,cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R,cytochalasin S, chaetoglobosin A, chaetoglobosin B, chaetoglobosin C,chaetoglobosin D, chaetoglobosin E, chaetoglobosin F, chaetoglobosin G,chaetoglobosin J, chaetoglobosin K, deoxaphomin, proxiphomin,protophomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G,aspochalasin B, aspochalasin C, aspochalasin D, etc.), paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF(granulo-cyte-macrophage colony-stimulating-factor), GM-CSF derivatives,or combinations thereof. In one non-limiting embodiment of theinvention, the medical device can be partially of fully coated with oneor more biological agents, impregnated with one or more biologicalagents to facilitate in the success of a particular medical procedure.The one or more biological agents can be coated on and/or impregnated inthe medical device by a variety of mechanisms such as, but not limitedto, spraying (e.g., atomizing spray techniques, etc.), dip coating, rollcoating, sonication, brushing, plasma deposition, depositing by vapordeposition. In another and/or alternative non-limiting embodiment of theinvention, the type and/or amount of biological agent included on, inand/or in conjunction with the medical device is generally selected forthe treatment of one or more medical treatments. Typically, the amountof biological agent included on, in and/or used in conjunction with themedical device is about 0.01-100 ug per mm²; however, other amounts canbe used. The amount of two or more biological agents on, in and/or usedin conjunction with the medical device can be the same or different. Forinstance, one or more biological agents can be coated on, and/orincorporated in one or more portions of the medical device to providelocal and/or systemic delivery of one or more biological agents inand/or to a body passageway to a) inhibit or prevent thrombosis,in-stent restenosis, vascular narrowing and/or restenosis after themedical device has been inserted in and/or connected to a bodypassageway, b) at least partially passivate, remove and/or dissolvelipids, fibroblast, fibrin, etc. in a body passageway so as to at leastpartially remove such materials and/or to passivate such vulnerablematerials (e.g., vulnerable plaque, etc.) in the body passageway in theregion of the medical device and/or down stream of the medical device.As can be appreciated, the one or more biological agents can have manyother or additional uses. In another and/or alternative non-limitingexample, the medical device is coated with and/or includes one or morebiological agents such as, but not limited to, trapidil and/or trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. In still anotherand/or alternative non-limiting example, the medical device is coatedwith and/or includes one or more biological agents such as, but notlimited to trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof, and one or more additional biological agents, suchas, but not limited to, biological agents associated with thrombolytics,vasodilators, anti-hypertensive agents, anti-microbial or anti-biotic,anti-mitotic, anti-proliferative, anti-secretory agents, non-steroidalanti-inflammatory drugs, immunosuppressive agents, growth factors andgrowth factor antagonists, antitumor and/or chemotherapeutic agents,anti-polymerases, anti-viral agents, anti-body targeted therapy agents,hormones, anti-oxidants, biologic components, radio-therapeutic agents,radiopaque agents and/or radio-labeled agents. In addition to thesebiological agents, the medical device can be coated with and/or includeone or more biological agents that are capable of inhibiting orpreventing any adverse biological response by and/or to the medicaldevice that could possibly lead to device failure and/or an adversereaction by human or animal tissue. A wide range of biological agentsthus can be used.

In a further and/or alternative non-limiting aspect of the presentinvention, the one or more biological agents on and/or in the medicaldevice, when used on the medical device, can be released in a controlledmanner so the area in question to be treated is provided with thedesired dosage of biological agent over a sustained period of time. Ascan be appreciated, controlled release of one or more biological agentson the medical device is not always required and/or desirable. As such,one or more of the biological agents on and/or in the medical device canbe uncontrollably released from the medical device during and/or afterinsertion of the medical device in the treatment area. It can also beappreciated that one or more biological agents on and/or in the medicaldevice can be controllably released from the medical device and one ormore biological agents on and/or in the medical device can beuncontrollably released from the medical device. It can also beappreciated that one or more biological agents on and/or in one regionof the medical device can be controllably released from the medicaldevice and one or more biological agents on and/or in the medical devicecan be uncontrollably released from another region on the medicaldevice. As such, the medical device can be designed such that 1) all thebiological agent on and/or in the medical device is controllablyreleased, 2) some of the biological agent on and/or in the medicaldevice is controllably released and some of the biological agent on themedical device is non-controllably released, or 3) none of thebiological agent on and/or in the medical device is controllablyreleased. The medical device can also be designed such that the rate ofrelease of the one or more biological agents from the medical device isthe same or different. The medical device can also be designed such thatthe rate of release of the one or more biological agents from one ormore regions on the medical device is the same or different.Non-limiting arrangements that can be used to control the release of oneor more biological agent from the medical device include a) at leastpartially coat one or more biological agents with one or more polymers,b) at least partially incorporate and/or at least partially encapsulateone or more biological agents into and/or with one or more polymers,and/or c) insert one or more biological agents in pores, passageway,cavities, etc. in the medical device and at least partially coat orcover such pores, passageway, cavities, etc. with one or more polymers.As can be appreciated, other or additional arrangements can be used tocontrol the release of one or more biological agent from the medicaldevice. The one or more polymers used to at least partially control therelease of one or more biological agent from the medical device can beporous or non-porous. The one or more biological agents can be insertedinto and/or applied to one or more surface structures and/ormicro-structures on the medical device, and/or be used to at leastpartially form one or more surface structures and/or micro-structures onthe medical device. As such, the one or more biological agents on themedical device can be 1) coated on one or more surface regions of themedical device, 2) inserted and/or impregnated in one or more surfacestructures and/or micro-structures, etc. of the medical device, and/or3) form at least a portion or be included in at least a portion of thestructure of the medical device. When the one or more biological agentsare coated on the medical device, the one or more biological agentscan 1) be directly coated on one or more surfaces of the medical device,2) be mixed with one or more coating polymers or other coating materialsand then at least partially coated on one or more surfaces of themedical device, 3) be at least partially coated on the surface ofanother coating material that has been at least partially coated on themedical device, and/or 4) be at least partially encapsulated between a)a surface or region of the medical device and one or more other coatingmaterials and/or b) two or more other coating materials. As can beappreciated, many other coating arrangements can be additionally oralternatively used. When the one or more biological agents are insertedand/or impregnated in one or more internal structures, surfacestructures and/or micro-structures of the medical device, 1) one or moreother coating materials can be applied at least partially over the oneor more internal structures, surface structures and/or micro-structuresof the medical device, and/or 2) one or more polymers can be combinedwith one or more biological agents. As such, the one or more biologicalagents can be 1) embedded in the structure of the medical device; 2)positioned in one or more internal structures of the medical device; 3)encapsulated between two polymer coatings; 4) encapsulated between thebase structure and a polymer coating; 5) mixed in the base structure ofthe medical device that includes at least one polymer coating; or 6) oneor more combinations of 1, 2, 3, 4 and/or 5. In addition oralternatively, the one or more coating of the one or more polymers onthe medical device can include 1) one or more coatings of non-porouspolymers; 2) one or more coatings of a combination of one or more porouspolymers and one or more non-porous polymers; 3) one or more coating ofporous polymer, or 4) one or more combinations of options 1, 2, and 3.As can be appreciated different biological agents can be located inand/or between different polymer coating layers and/or on and/or thestructure of the medical device. As can also be appreciated, many otherand/or additional coating combinations and/or configurations can beused. The concentration of one or more biological agents, the type ofpolymer, the type and/or shape of internal structures in the medicaldevice and/or the coating thickness of one or more biological agents canbe used to control the release time, the release rate and/or the dosageamount of one or more biological agents; however, other or additionalcombinations can be used. As such, the biological agent and polymersystem combination and location on the medical device can be numerous.As can also be appreciated, one or more biological agents can bedeposited on the top surface of the medical device to provide an initialuncontrolled burst effect of the one or more biological agents priorto 1) the control release of the one or more biological agents throughone or more layers of polymer system that include one or more non-porouspolymers and/or 2) the uncontrolled release of the one or morebiological agents through one or more layers of polymer system. The oneor more biological agents and/or polymers can be coated on the medicaldevice by a variety of mechanisms such as, but not limited to, spraying(e.g., atomizing spray techniques, etc.), dip coating, roll coating,sonication, brushing, plasma deposition, and/or depositing by vapordeposition. The thickness of each polymer layer and/or layer ofbiological agent is generally at least about 0.01 μm and is generallyless than about 150 μm. In one non-limiting embodiment, the thickness ofa polymer layer and/or layer of biological agent is about 0.02-75 μm,more particularly about 0.05-50 μm, and even more particularly about1-30 μm. When the medical device includes and/or is coated with one ormore biological agents such that at least one of the biological agentsis at least partially controllably released from the medical device, theneed or use of body-wide therapy for extended periods of time can bereduced or eliminated. In the past, the use of body-wide therapy wasused by the patient long after the patient left the hospital or othertype of medical facility. This body-wide therapy could last days, weeks,months or sometimes over a year after surgery. The medical device of thepresent invention can be applied or inserted into a treatment areaand 1) merely requires reduced use and/or extended use of body widetherapy after application or insertion of the medical device or 2) doesnot require use and/or extended use of body-wide therapy afterapplication or insertion of the medical device. As can be appreciated,use and/or extended use of body wide therapy can be used afterapplication or insertion of the medical device at the treatment area. Inone non-limiting example, no body-wide therapy is needed after theinsertion of the medical device into a patient. In another and/oralternative non-limiting example, short term use of body-wide therapy isneeded or used after the insertion of the medical device into a patient.Such short term use can be terminated after the release of the patientfrom the hospital or other type of medical facility, or one to two daysor weeks after the release of the patient from the hospital or othertype of medical facility; however, it will be appreciated that othertime periods of body-wide therapy can be used. As a result of the use ofthe medical device of the present invention, the use of body-widetherapy after a medical procedure involving the insertion of a medicaldevice into a treatment area can be significantly reduced or eliminated.

In another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more non-porous polymer layers; however, other and/oradditional mechanisms can be used to controllably release the one ormore biological agents. The one or more biological agents are at leastpartially controllably released by molecular diffusion through the oneor more non-porous polymer layers. When one or more non-porous polymerlayers are used, the one or more polymer layers are typicallybiocompatible polymers; however, this is not required. The one or morenon-porous polymers can be applied to the medical device without the useof chemical, solvents, and/or catalysts; however, this is not required.In one non-limiting example, the non-porous polymer can be at leastpartially applied by, but not limited to, vapor deposition and/or plasmadeposition. The non-porous polymer can be selected so as to polymerizeand cure merely upon condensation from the vapor phase; however, this isnot required. The application of the one or more non-porous polymerlayers can be accomplished without increasing the temperature aboveambient temperature (e.g., 65-90° F.); however, this is not required.The non-porous polymer system can be mixed with one or more biologicalagents prior to being coated on the medical device and/or be coated on amedical device that previously included one or more biological agents;however, this is not required. The use or one or more non-porous polymerlayers allow for accurate controlled release of the biological agentfrom the medical device. The controlled release of one or morebiological agents through the non-porous polymer is at least partiallycontrolled on a molecular level utilizing the motility of diffusion ofthe biological agent through the non-porous polymer. In one non-limitingexample, the one or more non-porous polymer layers can include, but arenot limited to, polyamide, parylene (e.g., parylene C, parylene N)and/or a parylene derivative.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more polymers that form a chemical bond with one or morebiological agents. In one non-limiting example, at least one biologicalagent includes trapidil, trapidil derivative or a salt thereof that iscovalently bonded to at least one polymer such as, but not limited to,an ethylene-acrylic acid copolymer. The ethylene is the hydrophobicgroup and acrylic acid is the hydrophilic group. The mole ratio of theethylene to the acrylic acid in the copolymer can be used to control thehydrophobicity of the copolymer. The degree of hydrophobicity of one ormore polymers can also be used to control the release rate of one ormore biological agents from the one or more polymers. The amount ofbiological agent that can be loaded with one or more polymers may be afunction of the concentration of anionic groups and/or cationic groupsin the one or more polymer. For biological agents that are anionic, theconcentration of biological agent that can be loaded on the one or morepolymers is generally a function of the concentration of cationic groups(e.g. amine groups and the like) in the one or more polymer and thefraction of these cationic groups that can ionically bind to the anionicform of the one or more biological agents. For biological agents thatare cationic (e.g., trapidil, etc.), the concentration of biologicalagent that can be loaded on the one or more polymers is generally afunction of the concentration of anionic groups (i.e., carboxylategroups, phosphate groups, sulfate groups, and/or other organic anionicgroups) in the one or more polymers, and the fraction of these anionicgroups that can ionically bind to the cationic form of the one or morebiological agents. As such, the concentration of one or more biologicalagent that can be bound to the one or more polymers can be varied bycontrolling the amount of hydrophobic and hydrophilic monomer in the oneor more polymers, by controlling the efficiency of salt formationbetween the biological agent, and/or the anionic/cationic groups in theone or more polymers.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more polymers that include one or more inducedcross-links. These one or more cross-links can be used to at leastpartially control the rate of release of the one or more biologicalagents from the one or more polymers. The cross-linking in the one ormore polymers can be instituted by a number to techniques such as, butnot limited to, using catalysts, using radiation, using heat, and/or thelike. The one or more cross-links formed in the one or more polymers canresult in the one or more biological agents to become partially or fullyentrapped within the cross-linking, and/or form a bond with thecross-linking. As such, the partially or fully biological agent takeslonger to release itself from the cross-linking, thereby delaying therelease rate of the one or more biological agents from the one or morepolymers. Consequently, the amount of biological agent, and/or the rateat which the biological agent is released from the medical device overtime can be at least partially controlled by the amount or degree ofcross-linking in the one or more polymers.

In still a further and/or alternative aspect of the present invention, avariety of polymers can be coated on the medical device and/or be usedto form at least a portion of the medical device. The one or morepolymers can be used on the medical for a variety of reasons such as,but not limited to, 1) forming a portion of the medical device, 2)improving a physical property of the medical device (e.g., improvestrength, improve durability, improve biocompatibility, reduce friction,etc.), 3) forming a protective coating on one or more surface structureson the medical device, 4) at least partially forming one or more surfacestructures on the medical device, and/or 5) at least partiallycontrolling a release rate of one or more biological agents from themedical device. As can be appreciated, the one or more polymers can haveother or additional uses on the medical device. The one or more polymerscan be porous, non-porous, biostable, biodegradable (i.e., dissolves,degrades, is absorbed, or any combination thereof in the body), and/orbiocompatible. When the medical device is coated with one or morepolymers, the polymer can include 1) one or more coatings of non-porouspolymers; 2) one or more coatings of a combination of one or more porouspolymers and one or more non-porous polymers; 3) one or more coatings ofone or more porous polymers and one or more coatings of one or morenon-porous polymers; 4) one or more coating of porous polymer, or 5) oneor more combinations of options 1, 2, 3 and 4. The thickness of one ormore of the polymer layers can be the same or different. When one ormore layers of polymer are coated onto at least a portion of the medicaldevice, the one or more coatings can be applied by a variety oftechniques such as, but not limited to, vapor deposition and/or plasmadeposition, spraying, dip-coating, roll coating, sonication,atomization, brushing and/or the like; however, other or additionalcoating techniques can be used. The one or more polymers that can becoated on the medical device and/or used to at least partially form themedical device can be polymers that considered to be biodegradable,bioresorbable, or bioerodable; polymers that are considered to bebiostable; and/or polymers that can be made to be biodegradable and/orbioresorbable with modification. Non-limiting examples of polymers thatare considered to be biodegradable, bioresorbable, or bioerodableinclude, but are not limited to, aliphatic polyesters; poly(glycolicacid) and/or copolymers thereof (e.g., poly(glycolide trimethylenecarbonate); poly(caprolactone glycolide)); poly(lactic acid) and/orisomers thereof (e.g., poly-L(lactic acid) and/or poly-D Lactic acid)and/or copolymers thereof (e.g. DL-PLA), with and without additives(e.g. calcium phosphate glass), and/or other copolymers (e.g.poly(caprolactone lactide), poly(lactide glycolide), poly(lactic acidethylene glycol)); poly(ethylene glycol); poly(ethylene glycol)diacrylate; poly(lactide); polyalkylene succinate; polybutylenediglycolate; polyhydroxybutyrate (PHB); polyhydroxyvalerate (PHV);polyhydroxybutyrate/polyhydroxyvalerate copolymer (PHB/PHV);poly(hydroxybutyrate-co-valerate); polyhydroxyalkaoates (PHA);polycaprolactone; poly(caprolactone-polyethylene glycol) copolymer;poly(valerolactone); polyanhydrides; poly(orthoesters) and/or blendswith polyanhydrides; poly(anhydride-co-imide); polycarbonates(aliphatic); poly(hydroxyl-esters); polydioxanone; polyanhydrides;polyanhydride esters; polycyanoacrylates; poly(alkyl 2-cyanoacrylates);poly(amino acids); poly(phosphazenes); poly(propylene fumarate);poly(propylene fumarate-co-ethylene glycol); poly(fumarate anhydrides);fibrinogen; fibrin; gelatin; cellulose and/or cellulose derivativesand/or cellulosic polymers (e.g., cellulose acetate, cellulose acetatebutyrate, cellulose butyrate, cellulose ethers, cellulose nitrate,cellulose propionate, cellophane); chitosan and/or chitosan derivatives(e.g., chitosan NOCC, chitosan NOOC-G); alginate; polysaccharides;starch; amylase; collagen; polycarboxylic acids; poly(ethylester-co-carboxylate carbonate) (and/or other tyrosine derivedpolycarbonates); poly(iminocarbonate); poly(BPA-iminocarbonate);poly(trimethylene carbonate); poly(iminocarbonate-amide) copolymersand/or other pseudo-poly(amino acids); poly(ethylene glycol);poly(ethylene oxide); poly(ethylene oxide)/poly(butylene terephthalate)copolymer; poly(epsilon-caprolactone-dimethyltrimethylene carbonate);poly(ester amide); poly(amino acids) and conventional synthetic polymersthereof; poly(alkylene oxalates); poly(alkylcarbonate); poly(adipicanhydride); nylon copolyamides; NO-carboxymethyl chitosan NOCC);carboxymethyl cellulose; copoly(ether-esters) (e.g., PEO/PLA dextrans);polyketals; biodegradable polyethers; biodegradable polyesters;polydihydropyrans; polydepsipeptides; polyarylates (L-tyrosine-derived)and/or free acid polyarylates; polyamides (e.g., Nylon 66,polycaprolactam); poly(propylene fumarate-co-ethylene glycol) (e.g.,fumarate anhydrides); hyaluronates; poly-p-dioxanone; polypeptides andproteins; polyphosphoester; polyphosphoester urethane; polysaccharides;pseudo-poly(amino acids); starch; terpolymer; (copolymers of glycolide,lactide, or dimethyltrimethylene carbonate); rayon; rayon triacetate;latex; and/pr copolymers, blends, and/or composites of above.Non-limiting examples of polymers that considered to be biostableinclude, but are not limited to, parylene; parylene c; parylene f;parylene n; parylene derivatives; maleic anyhydride polymers;phosphorylcholine; poly n-butyl methacrylate (PBMA);polyethylene-co-vinyl acetate (PEVA); PBMA/PEVA blend or copolymer;polytetrafluoroethene (Teflon®) and derivatives; poly-paraphenyleneterephthalamide (Kevlar®); poly(ether ether ketone) (PEEK);poly(styrene-b-isobutylene-b-styrene) (Translute™);tetramethyldisiloxane (side chain or copolymer); polyimidespolysulfides; poly(ethylene terephthalate); poly(methyl methacrylate);poly(ethylene-co-methyl methacrylate); styrene-ethylene/butylene-styreneblock copolymers; ABS; SAN; acrylic polymers and/or copolymers (e.g.,n-butyl-acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate,lauryl-acrylate, 2-hydroxy-propyl acrylate, polyhydroxyethyl,methacrylate/methylmethacrylate copolymers); glycosaminoglycans; alkydresins; elastin; polyether sulfones; epoxy resin; poly(oxymethylene);polyolefins; polymers of silicone; polymers of methane; polyisobutylene;ethylene-alphaolefin copolymers; polyethylene; polyacrylonitrile;fluorosilicones; poly(propylene oxide); polyvinyl aromatics (e.g.polystyrene); poly(vinyl ethers) (e.g. polyvinyl methyl ether);poly(vinyl ketones); poly(vinylidene halides) (e.g. polyvinylidenefluoride, polyvinylidene chloride); poly(vinylpyrolidone);poly(vinylpyrolidone)/vinyl acetate copolymer; polyvinylpridineprolastin or silk-elastin polymers (SELP); silicone; silicone rubber;polyurethanes (polycarbonate polyurethanes, silicone urethane polymer)(e.g., chronoflex varieties, bionate varieties); vinyl halide polymersand/or copolymers (e.g. polyvinyl chloride); polyacrylic acid; ethyleneacrylic acid copolymer; ethylene vinyl acetate copolymer; polyvinylalcohol; poly(hydroxyl alkylmethacrylate); Polyvinyl esters (e.g.polyvinyl acetate); and/or copolymers, blends, and/or composites ofabove. Non-limiting examples of polymers that can be made to bebiodegradable and/or bioresorbable with modification include, but arenot limited to, hyaluronic acid (hyanluron); polycarbonates;polyorthocarbonates; copolymers of vinyl monomers; polyacetals;biodegradable polyurethanes; polyacrylamide; polyisocyanates; polyamide;and/or copolymers, blends, and/or composites of above. As can beappreciated, other and/or additional polymers and/or derivatives of oneor more of the above listed polymers can be used. The one or morepolymers can be coated on the medical device by a variety of mechanismssuch as, but not limited to, spraying (e.g., atomizing spray techniques,etc.), dip coating, roll coating, sonication, brushing, plasmadeposition, and/or depositing by vapor deposition. The thickness of eachpolymer layer is generally at least about 0.01 μm and is generally lessthan about 150 μm; however, other thicknesses can be used. In onenon-limiting embodiment, the thickness of a polymer layer and/or layerof biological agent is about 0.02-75 μm, more particularly about 0.05-50μm, and even more particularly about 1-30 μm. As can be appreciated,other thicknesses can be used. In one non-limiting embodiment, themedical device includes and/or is coated with parylene, PLGA, POE, PGA,PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesepolymers. In another and/or alternative non-limiting embodiment, themedical device includes and/or is coated with a non-porous polymer thatincludes, but is not limited to, polyamide, parylene c, parylene nand/or a parylene derivative. In still another and/or alternativenon-limiting embodiment, the medical device includes and/or is coatedwith poly(ethylene oxide), poly(ethylene glycol), and poly(propyleneoxide), polymers of silicone, methane, tetrafluoroethylene (includingTEFLON brand polymers), tetramethyldisiloxane, and the like.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device, when including and/or is coated with oneor more biological agents, can include and/or can be coated with one ormore biological agents that are the same or different in differentregions of the medical device and/or have differing amounts and/orconcentrations in differing regions of the medical device. For instance,the medical device can a) be coated with and/or include one or morebiologicals on at least one portion of the medical device and at leastanother portion of the medical device is not coated with and/or includesbiological agent; b) be coated with and/or include one or morebiologicals on at least one portion of the medical device that isdifferent from one or more biologicals on at least another portion ofthe medical device; c) be coated with and/or include one or morebiologicals at a concentration on at least one portion of the medicaldevice that is different from the concentration of one or morebiologicals on at least another portion of the medical device; etc.

In still another and/or alternative non-limiting aspect of the presentinvention, one or more surfaces of the medical device can be treated toachieve the desired coating properties of the one or more biologicalagents and one or more polymers coated on the medical device. Suchsurface treatment techniques include, but are not limited to, cleaning,buffing, smoothing, etching (chemical etching, plasma etching, etc.),etc. When an etching process is used, various gasses can be used forsuch a surface treatment process such as, but not limited to, carbondioxide, nitrogen, oxygen, Freon, helium, hydrogen, etc. The plasmaetching process can be used to clean the surface of the medical device,change the surface properties of the medical device so as to affect theadhesion properties, lubricity properties, etc. of the surface of themedical device. As can be appreciated, other or additional surfacetreatment processes can be used prior to the coating of one or morebiological agents and/or polymers on the surface of the medical device.In one non-limiting manufacturing process, one or more portions of themedical device are cleaned and/or plasma etched; however, this is notrequired. Plasma etching can be used to clean the surface of the medicaldevice, and/or to form one or more non-smooth surfaces on the medicaldevice to facilitate in the adhesion of one or more coatings ofbiological agents and/or one or more coatings of polymer on the medicaldevice. The gas for the plasma etching can include carbon dioxide and/orother gasses. Once one or more surface regions of the medical devicehave been treated, one or more coatings of polymer and/or biologicalagent can be applied to one or more regions of the medical device. Forinstance, 1) one or more layers of porous or non-porous polymer can becoated on an outer and/or inner surface of the medical device, 2) one ormore layers of biological agent can be coated on an outer and/or innersurface of the medical device, or 3) one or more layers of porous ornon-porous polymer that includes one or more biological agents can becoated on an outer and/or inner surface of the medical device. The oneor more layers of biological agent can be applied to the medical deviceby a variety of techniques (e.g., dipping, rolling, brushing, spraying,particle atomization, etc.). One non-limiting coating technique is by anultrasonic mist coating process wherein ultrasonic waves are used tobreak up the droplet of biological agent and form a mist of very finedroplets. These fine droplets have an average droplet diameter of about0.1-3 microns. The fine droplet mist facilitates in the formation of auniform coating thickness and can increase the coverage area on themedical device.

In still yet another and/or alternative non-limiting aspect of thepresent invention, one or more portions of the medical device can 1)include the same or different biological agents, 2) include the same ordifferent amount of one or more biological agents, 3) include the sameor different polymer coatings, 4) include the same or different coatingthicknesses of one or more polymer coatings, 5) have one or moreportions of the medical device controllably release and/oruncontrollably release one or more biological agents, and/or 6) have oneor more portions of the medical device controllably release one or morebiological agents and one or more portions of the medical deviceuncontrollably release one or more biological agents.

In yet another and/or alternative non-limiting aspect of the invention,the medical device can include a marker material that facilitatesenabling the medical device to be properly positioned in a bodypassageway. The marker material is typically designed to be visible toelectromagnetic waves (e.g., x-rays, microwaves, visible light, inferredwaves, ultraviolet waves, etc.); sound waves (e.g., ultrasound waves,etc.); magnetic waves (e.g., MRI, etc.); and/or other types ofelectromagnetic waves (e.g., microwaves, visible light, inferred waves,ultraviolet waves, etc.). In one non-limiting embodiment, the markermaterial is visible to x-rays (i.e., radiopaque). The marker materialcan form all or a portion of the medical device and/or be coated on oneor more portions (flaring portion and/or body portion; at ends ofmedical device; at or near transition of body portion and flaringsection; etc.) of the medical device. The location of the markermaterial can be on one or multiple locations on the medical device. Thesize of the one or more regions that include the marker material can bethe same or different. The marker material can be spaced at defineddistances from one another so as to form ruler like markings on themedical device to facilitate in the positioning of the medical device ina body passageway. The marker material can be a rigid or flexiblematerial. The marker material can be a biostable or biodegradablematerial. When the marker material is a rigid material, the markermaterial is typically formed of a metal material (e.g., metal band,metal plating, etc.); however, other or additional materials can beused. The metal which at least partially forms the medical device canfunction as a marker material; however, this is not required. When themarker material is a flexible material, the marker material typically isformed of one or more polymers that are marker materialsin-of-themselves and/or include one or more metal powders and/or metalcompounds. In one non-limiting embodiment, the flexible marker materialincludes one or more metal powders in combinations with parylene, PLGA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers. In another and/or alternative non-limiting embodiment,the flexible marker material includes one or more metals and/or metalpowders of aluminum, barium, bismuth, cobalt, copper, chromium, gold,iron, stainless steel, titanium, vanadium, nickel, zirconium, niobium,lead, molybdenum, platinum, yttrium, calcium, rare earth metals,rhenium, zinc, silver, depleted radioactive elements, tantalum and/ortungsten; and/or compounds thereof. The marker material can be coatedwith a polymer protective material; however, this is not required. Whenthe marker material is coated with a polymer protective material, thepolymer coating can be used to 1) at least partially insulate the markermaterial from body fluids, 2) facilitate in retaining the markermaterial on the medical device, 3) at least partially shielding themarker material from damage during a medical procedure and/or 4) providea desired surface profile on the medical device. As can be appreciated,the polymer coating can have other or additional uses. The polymerprotective coating can be a biostable polymer or a biodegradable polymer(e.g., degrades and/or is absorbed). The coating thickness of theprotective coating polymer material, when used, is typically less thanabout 300 microns; however, other thickness can be used. In onenon-limiting embodiment, the protective coating materials includeparylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives ofone or more of these polymers.

In a further and/or alternative non-limiting aspect of the presentinvention, the medical device or one or more regions of the medicaldevice can be constructed by use of one or more microelectromechanicalmanufacturing techniques (MEMS (e.g., micro-machining, lasermicro-machining, laser micro-machining, micro-molding, etc.); however,other or additional manufacturing techniques can be used. The medicaldevice can include one or more surface structures (e.g., pore, channel,pit, rib, slot, notch, bump, teeth, needle, well, hole, groove, etc.).These structures can be at least partially formed by MEMS (e.g.,micro-machining, etc.) technology and/or other types of technology. Themedical device can include one or more micro-structures (e.g.,micro-needle, micro-pore, micro-cylinder, micro-cone, micro-pyramid,micro-tube, micro-parallelopiped, micro-prism, micro-hemisphere, teeth,rib, ridge, ratchet, hinge, zipper, zip-tie like structure, etc.) on thesurface of the medical device. As defined herein, a micro-structure is astructure that has at least one dimension (e.g., average width, averagediameter, average height, average length, average depth, etc.) that isno more than about 2 mm, and typically no more than about 1 mm. As canbe appreciated, the medical device, when including one or more surfacestructures, a) all the surface structures can be micro-structures, b)all the surface structures can be non-micro-structures, or c) a portionof the surface structures can be micro-structures and a portion can benon-micro-structures. Non-limiting examples of structures that can beformed on the medical devices such as stents are illustrated in UnitedStates Patent Publication Nos. 2004/0093076 and 2004/0093077, which areincorporated herein by reference. Typically, the micro-structures, whenformed, extend from or into the outer surface no more than about 400microns, and more typically less than about 300 microns, and moretypically about 15-250 microns; however, other sizes can be used. Themicro-structures can be clustered together or disbursed throughout thesurface of the medical device. Similar shaped and/or sizedmicro-structures and/or surface structures can be used, or differentshaped and/or sized micro-structures can be used. When one or moresurface structures and/or micro-structures are designed to extend fromthe surface of the medical device, the one or more surface structuresand/or micro-structures can be formed in the extended position and/or bedesigned so as to extend from the medical device during and/or afterdeployment of the medical device in a treatment area. Themicro-structures and/or surface structures can be designed to containand/or be fluidly connected to a passageway, cavity, etc.; however, thisis not required. The one or more surface structures and/ormicro-structures can be used to engage and/or penetrate surroundingtissue or organs once the medical device has be position on and/or in apatient; however, this is not required. The one or more surfacestructures and/or micro-structures can be used to facilitate in formingmaintaining a shape of a medical device (i.e., see devices in UnitedStates Patent Publication Nos. 2004/0093076 and 2004/0093077). The oneor more surface structures and/or micro-structures can be at leastpartially formed by MEMS (e.g., micro-machining, laser micro-machining,micro-molding, etc.) technology; however, this is not required. In onenon-limiting embodiment, the one or more surface structures and/ormicro-structures can be at least partially formed of a biological agentand/or be formed of a polymer. One or more of the surface structuresand/or micro-structures can include one or more internal passagewaysthat can include one or more materials (e.g., biological agent, polymer,etc.); however, this is not required. The one or more surface structuresand/or micro-structures can be formed by a variety of processes (e.g.,machining, chemical modifications, chemical reactions, MEMS (e.g.,micro-machining, etc.), etching, laser cutting, etc.). The one or morecoatings and/or one or more surface structures and/or micro-structuresof the medical device can be used for a variety of purposes such as, butnot limited to, 1) increasing the bonding and/or adhesion of one or morebiological agents, adhesives, marker materials and/or polymers to themedical device, 2) changing the appearance or surface characteristics ofthe medical device, and/or 3) controlling the release rate of one ormore biological agents. The one or more micro-structures and/or surfacestructures can be biostable, biodegradable, etc. One or more regions ofthe medical device that are at least partially formed bymicroelectromechanical manufacturing techniques can be biostable,biodegradable, etc. The medical device or one or more regions of themedical device can be at least partially covered and/or filled with aprotective material so to at least partially protect one or more regionsof the medical device, and/or one or more micro-structures and/orsurface structures on the medical device from damage. One or moreregions of the medical device, and/or one or more micro-structuresand/or surface structures on the medical device can be damaged when themedical device is 1) packaged and/or stored, 2) unpackaged, 3) connectedto and/or other secured and/or placed on another medical device, 4)inserted into a treatment area, 5) handled by a user, and/or 6) form abarrier between one or more micro-structures and/or surface structuresand fluids in the body passageway. As can be appreciated, the medicaldevice can be damaged in other or additional ways. The protectivematerial can be used to protect the medical device and one or moremicro-structures and/or surface structures from such damage. Theprotective material can include one or more polymers previouslyidentified above. The protective material can be 1) biostable and/orbiodegradable and/or 2) porous and/or non-porous. In one non-limitingdesign, the polymer is at least partially biodegradable so as to atleast partially exposed one or more micro-structure and/or surfacestructure to the environment after the medical device has been at leastpartially inserted into a treatment area. In another and/or additionalnon-limiting design, the protective material includes, but is notlimited to, sugar (e.g., glucose, fructose, sucrose, etc.), carbohydratecompound, salt (e.g., NaCl, etc.), parylene, PLGA, POE, PGA, PLLA, PAA,PEG, chitosan and/or derivatives of one or more of these materials;however, other and/or additional materials can be used. In still anotherand/or additional non-limiting design, the thickness of the protectivematerial is generally less than about 300 microns, and typically lessthan about 150 microns; however, other thicknesses can be used. Theprotective material can be coated by one or more mechanisms previouslydescribed herein.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the medical device can include and/or be used with aphysical hindrance. The physical hindrance can include, but is notlimited to, an adhesive, a sheath, a magnet, tape, wire, string, etc.The physical hindrance can be used to 1) physically retain one or moreregions of the medical device in a particular form or profile, 2)physically retain the medical device on a particular deployment device,3) protect one or more surface structures and/or micro-structures on themedical device, and/or 4) form carrier between one or more surfaceregions, surface structures and/or micro-structures on the medicaldevice and the fluids in a body passageway. As can be appreciated, thephysical hindrance can have other and/or additional functions. Thephysical hindrance is typically a biodegradable material; however, abiostable material can be used. The physical hindrance can be designedto withstand sterilization of the medical device; however, this is notrequired. The physical hindrance can be applied to, included in and/orbe used in conjunction with one or more medical devices. Additionally oralternatively, the physical hindrance can be designed to be used withand/or conjunction with a medical device for a limited period of timeand then 1) disengage from the medical device after the medical devicehas been partially or fully deployed and/or 2) dissolve and/or degradeduring and/or after the medical device has been partially or fullydeployed; however, this is not required. Additionally or alternatively,the physical hindrance can be designed and be formulated to betemporarily used with a medical device to facilitate in the deploymentof the medical device; however, this is not required. In onenon-limiting use of the physical hindrance, the physical hindrance isdesigned or formulated to at least partially secure a medical device toanother device that is used to at least partially transport the medicaldevice to a location for treatment. In another and/or alternativenon-limiting use of the physical hindrance, the physical hindrance isdesigned or formulated to at least partially maintain the medical devicein a particular shape or form until the medical device is at leastpartially positioned in a treatment location. In still another and/oralternative non-limiting use of the physical hindrance, the physicalhindrance is designed or formulated to at least partially maintainand/or secure one type of medical device to another type of medicalinstrument or device until the medical device is at least partiallypositioned in a treatment location. The physical hindrance can also oralternatively be designed and formulated to be used with a medicaldevice to facilitate in the use of the medical device. In onenon-limiting use of the physical hindrance, when in the form of anadhesive, can be formulated to at least partially secure a medicaldevice to a treatment area so as to facilitate in maintaining themedical device at the treatment area. For instance, the physicalhindrance can be used in such use to facilitate in maintaining a medicaldevice on or at a treatment area until the medical device is properlysecured to the treatment area by sutures, stitches, screws, nails, rod,etc; however, this is not required. Additionally or alternatively, thephysical hindrance can be used to facilitate in maintaining a medicaldevice on or at a treatment area until the medical device has partiallyor fully accomplished its objective. The physical hindrance is typicallya biocompatible material so as to not cause unanticipated adverseeffects when properly used. The physical hindrance can be biostable orbiodegradable (e.g., degrades and/or is absorbed, etc.). When thephysical hindrance includes or has one or more adhesives, the one ormore adhesives can be applied to the medical device by, but is notlimited to, spraying (e.g., atomizing spray techniques, etc.), dipcoating, roll coating, sonication, brushing, plasma deposition, and/ordepositing by vapor deposition, brushing, painting, etc.) on the medicaldevice. The physical hindrance can also or alternatively form at least apart of the medical device. One or more regions and/or surfaces of amedical device can also or alternatively include the physical hindrance.The physical hindrance can include one or more biological agents and/orother materials (e.g., marker material, polymer, etc.); however, this isnot required. When the physical hindrance is or includes an adhesive,the adhesive can be formulated to controllably release one or morebiological agents in the adhesive and/or coated on and/or containedwithin the medical device; however, this is not required. The adhesivecan also or alternatively control the release of one or more biologicalagents located on and/or contained in the medical device by forming apenetrable or non-penetrable barrier to such biological agents; however,this is not required. The adhesive can include and/or be mixed with oneor more polymers; however, this is not required. The one or morepolymers can be used to 1) control the time of adhesion provided by saidadhesive, 2) control the rate of degradation of the adhesive, and/or 3)control the rate of release of one or more biological agents from theadhesive and/or diffusing or penetrating through the adhesive layer;however, this is not required. When the physical hindrance includes asheath, the sheath can be designed to partially or fully encircle themedical device. The sheath can be designed to be physically removed fromthe medical device after the medical device is deployed to a treatmentarea; however, this is not required. The sheath can be formed of abiodegradable material that at least partially degrades over time to atleast partially expose one or more surface regions, micro-structuresand/or surface structures of the medical device; however, this is notrequired. The sheath can include and/or be at least partially coatedwith one or more biological agents. The sheath includes one or morepolymers; however, this is not required. The one or more polymers can beused for a variety of reasons such as, but not limited to, 1) forming aportion of the sheath, 2) improving a physical property of the sheath(e.g., improve strength, improve durability, improve biocompatibility,reduce friction, etc.), and/or 3 at least partially controlling arelease rate of one or more biological agents from the sheath. As can beappreciated, the one or more polymers can have other or additional useson the sheath.

In another and/or alternative non-limiting aspect of the invention, themedical device can include a biostable construction. In such a design,the medical device has two or more stable configurations, including afirst stable configuration with a first cross-sectional shape and asecond stable configuration with a second cross-sectional shape. All ora portion of the medical device can include the biostable construction.The bistable construction can result in a generally uniform change inshape of the medical device, or one portion of the medical device canchange into one or more configurations and one or more other portions ofthe medical device can change into one or more other configurations.

In still another and/or alternative aspect of the invention, the stentcan be an expandable device that can be expanded by use of some otherdevice (e.g., balloon, etc.) and/or is self expanding. The expandablestent can be fabricated from a material that has no or substantially noshape memory characteristics or can be partially fabricated from amaterial having shape-memory characteristics. Typically, when one ormore shape-memory materials are used, the shape memory materialcomposition is selected such that the shape memory material remains inan unexpanded configuration at a cold temperature (e.g., below bodytemperature); however, this is not required. When the shape memorymaterial is heated (e.g., to body temperature) the expandable bodysection can be designed to expand to at least partially seal and securethe stent in a body passageway or other region; however, this is notrequired.

In still another and/or alternative non-limiting aspect of theinvention, the medical device can be used in conjunction with one ormore other biological agents that are not on the medical device. Forinstance, the success of the medical device can be improved by infusing,injecting or consuming orally one or more biological agents. Suchbiological agents can be the same and/or different from the one or morebiological agents on and/or in the medical device. Such use of one ormore biological agents are commonly used in systemic treatment of apatient after a medical procedure such as body wide after the medicaldevice has been inserted in the treatment area can be reduced oreliminated by use of the novel alloy. Although the medical device of thepresent invention can be designed to reduce or eliminate the need forlong periods of body wide therapy after the medical device has beeninserted in the treatment area, the use of one or more biological agentscan be used in conjunction with the medical device to enhance thesuccess of the medical device and/or reduce or prevent the occurrence ofone or more biological problems (e.g., in-stent restenosis, vascularnarrowing, thrombosis, infection, rejection of the medical device,etc.). For instance, solid dosage forms of biological agents for oraladministration, and/or for other types of administration (e.g.,suppositories, etc.) can be used. Such solid forms can include, but arenot limited to, capsules, tablets, effervescent tablets, chewabletablets, pills, powders, sachets, granules and gels. The solid form ofthe capsules, tablets, effervescent tablets, chewable tablets, pills,etc. can have a variety of shapes such as, but not limited to,spherical, cubical, cylindrical, pyramidal, and the like. In such soliddosage form, one or more biological agents can be admixed with at leastone filler material such as, but not limited to, sucrose, lactose orstarch; however, this is not required. Such dosage forms can includeadditional substances such as, but not limited to, inert diluents (e.g.,lubricating agents, etc.). When capsules, tablets, effervescent tabletsor pills are used, the dosage form can also include buffering agents;however, this is not required. Soft gelatin capsules can be prepared tocontain a mixture of the one or more biological agents in combinationwith vegetable oil or other types of oil; however, this is not required.Hard gelatin capsules can contain granules of the one or more biologicalagents in combination with a solid carrier such as, but not limited to,lactose, potato starch, corn starch, cellulose derivatives of gelatin,etc; however, this is not required. Tablets and pills can be preparedwith enteric coatings for additional time release characteristics;however, this is not required. Liquid dosage forms of the one or morebiological agents for oral administration can include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, elixirs, etc.;however, this is not required. In one non-limiting embodiment, when atleast a portion of one or more biological agents is inserted into atreatment area (e.g., gel form, paste form, etc.) and/or provided orally(e.g., pill, capsule, etc.) and/or anally (suppository, etc.), one ormore of the biological agents can be controllably released; however,this is not required. In one non-limiting example, one or morebiological agents can be given to a patient in solid dosage form and oneor more of such biological agents can be controllably released from suchsolid dosage forms. In another and/or alternative non-limiting exampletrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof aregiven to a patient prior to, during and/or after the insertion of themedical device in a treatment area. As can be appreciated, other oradditional biological agents can be used. Certain types of biologicalagents may be desirable to be present in a treated area for an extendedperiod of time in order to utilize the full or nearly full clinicalpotential the biological agent. For instance, trapidil and/or trapidilderivatives is a compound that has many clinical attributes including,but not limited to, anti-platelet effects, inhibition of smooth musclecells and monocytes, fibroblast proliferation and increased MAPK-1 whichin turn deactivates kinase, a vasodilator, etc. These attributes can beeffective in improving the success of a medical device that has beeninserted at a treatment area. In some situations, these positive effectsof trapidil and/or trapidil derivatives need to be prolonged in atreatment area in order to achieve complete clinical competency.Trapidil and/or trapidil derivatives have a half life in vivo of about2-4 hours with hepatic clearance of 48 hours. In order to utilize thefull clinical potential of trapidil and/or trapidil derivatives,trapidil and/or trapidil derivatives should be metabolized over anextended period of time without interruption; however, this is notrequired. By inserting trapidil and/or trapidil derivatives in a soliddosage form, the trapidil and/or trapidil derivatives could be releasedin a patient over extended periods of time in a controlled manner toachieve complete or nearly complete clinical competency of the trapidiland/or trapidil derivatives. In another and/or alternative non-limitingexample, one or more biological agents are at least partiallyencapsulated in one or more polymers. The one or more polymers can bebiodegradable, non-biodegradable, porous, and/or non-porous. When theone or more polymers are biodegradable, the rate of degradation of theone or more biodegradable polymers can be used to at least partiallycontrol the rate at which one or more biological agent that are releasedinto a body passageway and/or other parts of the body over time. The oneor more biological agents can be at least partially encapsulated withdifferent polymer coating thickness, different numbers of coatinglayers, and/or with different polymers to alter the rate at which one ormore biological agents are released in a body passageway and/or otherparts of the body over time. The rate of degradation of the polymer isprincipally a function of 1) the water permeability and solubility ofthe polymer, 2) chemical composition of the polymer and/or biologicalagent, 3) mechanism of hydrolysis of the polymer, 4) the biologicalagent encapsulated in the polymer, 5) the size, shape and surface volumeof the polymer, 6) porosity of the polymer, 7) the molecular weight ofthe polymer, 8) the degree of cross-linking in the polymer, 9) thedegree of chemical bonding between the polymer and biological agent,and/or 10) the structure of the polymer and/or biological agent. As canbe appreciated, other factors may also affect the rate of degradation ofthe polymer. When the one or more polymers are biostable, the rate atwhen the one or more biological agents are released from the biostablepolymer is a function of 1) the porosity of the polymer, 2) themolecular diffusion rate of the biological agent through the polymer, 3)the degree of cross-linking in the polymer, 4) the degree of chemicalbonding between the polymer and biological agent, 5) chemicalcomposition of the polymer and/or biological agent, 6) the biologicalagent encapsulated in the polymer, 7) the size, shape and surface volumeof the polymer, and/or 8) the structure of the polymer and/or biologicalagent. As can be appreciated, other factors may also affect the rate ofrelease of the one or more biological agents from the biostable polymer.Many different polymers can be used such as, but not limited to,aliphatic polyester compounds (e.g., PLA (i.e. poly(D, L-lactic acid),poly(L-lactic acid)), PLGA (i.e. poly(lactide-co-glycoside), etc.), POE,PEG, PLLA, parylene, chitosan and/or derivatives thereof. As can beappreciated, the at least partially encapsulated biological agent can beintroduced into a patient by means other than by oral introduction, suchas, but not limited to, injection, topical applications, intravenously,eye drops, nasal spray, surgical insertion, suppositories,intrarticularly, intraocularly, intranasally, intradermally,sublingually, intravesically, intrathecally, intraperitoneally,intracranially, intramuscularly, subcutaneously, directly at aparticular site, and the like.

In yet another and/or alternative non-limiting aspect of the invention,the medical device is in the form of a stent. The stent can be anexpandable stent that is expandable by a balloon and/or isself-expanding. The stent can have one or more body members. The one ormore body members can include first and second ends and a wall surfacedisposed between the first and second ends. Typically each body memberhas a first cross-sectional area which permits delivery of the bodymember into a body passageway, and a second, expanded cross-sectionalarea. The expansion of one or more body members of the stent can beaccomplished in a variety of manners. In one manner, one or more bodymembers are expanded to the second cross-sectional area by a radially,outwardly extending force applied at least partially from the interiorregion of the body member (e.g. by use of a balloon, etc.). The bodymember can include shape memory materials; however, this is notrequired. The second cross-sectional area of the stent can be fixed orvariable. The stent can be designed such that one or more body membersexpand while substantially retaining the original longitudinal length ofthe body member; however, this is not required. The one or more bodymembers can have a first cross-sectional shape that is generallycircular so as to form a substantially tubular body member; however, theone or more body members can have other cross-sectional shapes. When thestent includes two or more body members, the two or more body memberscan be connected together by at least one connector member. The stentcan include rounded, smooth and/or blunt surfaces to minimize and/orprevent potential damage to a body passageway as the stent is insertedinto a body passageway and/or expanded in a body passageway; however,this is not required. The stent can be treated with gamma, beta and/ore-beam radiation, and/or otherwise sterilized; however, this is notrequired. The stent is partially or fully formed from the novel metalalloy. The use of the novel metal alloy to form all or a portion of thestent can result in several advantages over stents formed from othermaterials. These advantages include, but are not limited to:

-   -   The novel metal alloy has increased strength as compared with        stainless steel or chromium-cobalt alloys, thus less quantity of        novel metal alloy can be used in the stent to achieve similar        strengths as compared to stents formed of different metals. As        such, the resulting stent can be made smaller and less bulky by        use of the novel metal alloy without sacrificing the strength        and durability of the stent. The stent can also have a smaller        profile, thus can be inserted into smaller areas, openings        and/or passageways. The increased strength of the novel metal        alloy also results in the increased radial strength of the        stent. For instance, the thickness of the walls of the stent        and/or the wires used to form the stent can be made thinner and        achieve a similar or improved radial strength as compared with        thicker walled stents formed of stainless steel or cobalt and        chromium alloy.    -   The novel metal alloy has improved stress-strain properties,        bendability properties, elongation properties and/or flexibility        properties of the stent as compared with stainless steel or        chromium-cobalt alloys, thus resulting in an increase life for        the stent. For instance, the stent can be used in regions that        subject the stent to repeated bending. Due to the improved        physical properties of the stent from the novel metal alloy, the        stent has improved resistance to fracturing in such frequent        bending environments. These improved physical properties at        least in part result from the composition of the novel metal        alloy; the grain size of the novel metal alloy; the carbon,        oxygen and nitrogen content of the novel metal alloy; and/or the        carbon/oxygen ratio of the novel metal alloy.    -   The novel metal alloy has a reduce the degree of recoil during        the crimping and/or expansion of the stent as compared with        stainless steel or chromium-cobalt alloys. The stent formed of        the novel metal alloy better maintains its crimped form and/or        better maintains its expanded form after expansion due to the        use of the novel metal alloy. As such, when the stent is to be        mounted onto a delivery device when the stent is crimped, the        stent better maintains its smaller profile during the insertion        of the stent in a body passageway. Also, the stent better        maintains its expanded profile after expansion so as to        facilitate in the success of the stent in the treatment area.    -   The novel metal alloy has improved radiopaque properties as        compared to standard materials such as stainless steel or        cobalt-chromium alloy, thus reducing or eliminating the need for        using marker materials on the stent. For instance, the novel        metal alloy is at least about 10-20% more radiopaque than        stainless steel or cobalt-chromium alloy.    -   The novel metal alloy is less of an irritant to the body than        stainless steel or cobalt-chromium alloy, thus can result in        reduced inflammation, faster healing, increased success rates of        the stent. When the stent is expanded in a body passageway, some        minor damage to the interior of the passageway can occur. When        the body begins to heal such minor damage, the body has less        adverse reaction to the presence of the novel metal alloy than        compared to other metals such as stainless steel or        cobalt-chromium alloy.

In one non-limiting application of the present invention, there isprovided a medical device that is at least partially formed of a novelmetal alloy. The novel metal alloy imparts one or more improved physicalcharacteristics to the medical device (e.g., strength, durability,hardness, biostability, bendability, coefficient of friction, radialstrength, flexibility, tensile strength, elongation, longitudinallengthening, stress-strain properties, improved recoil properties,radiopacity, heat sensitivity, biocapatability, etc.). The novel metalalloy includes at least about 95 weight percent rhenium and molybdenum.The medical device can be designed to release one or more biologicalagents in a controlled and/or uncontrolled fashion; however, this is notrequired. For instance, when the medical device includes one or morebiological agents, all of the biological agents on the medical devicecan be controllably released from the medical device, all of thebiological agent on the medical device can be uncontrollably releasedfrom the medical device, or some of the biological agent on the medicaldevice can be controllably released and some uncontrollably releasedfrom the medical device. The controlled release of the one or morebiological agents, when used, can be at least partially accomplished bymolecular diffusion through one or more non-porous polymer layers;however, it will be appreciated that other, or additional mechanism canbe used to control the rate of release of one or more biological agentsfrom one or more regions of the medical device. The medical device caninclude one or more layers of polymer and/or biological agent on thesurface structure of one or more regions of the medical device; however,this is not required. The one or more polymers, when used, can includeparylene (e.g., parylene C, parylene N), PLGA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers; however,other or additional polymers can be used. Many different biologicalagents can be used on the medical device. Such biological agents, whenused, can include, but not limited to, trapidil, trapidil derivatives,taxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof; however, it will be appreciatedthat other or additional biological agents can be used. The polymerand/or biological agent, when included on and/or forms a portion of themedical device, can be hydrophobic or hydrophilic so as to facilitate inthe controlled release of the one or more biological agents; however,this is not required. The thickness of the one or more polymer layers,when used, can be selected to facilitate in the controlled release ofthe one or more biological agents; however, this is not required. Themolecular weight and/or molecular structure of the one or morebiological agents and/or one or more polymer can be selected tofacilitate in the release of the one or more biological agents; however,this is not required. The medical device can have a variety ofapplications such as, but not limited to placement into the vascularsystem, esophagus, trachea, colon, biliary tract, or urinary tract;however, the medical device can have other applications. The medicaldevice can have one or more body members, wherein each body memberincludes first and second ends and a wall surface disposed between thefirst and second ends. Each body member can have a first cross-sectionalarea which permits delivery of the body member into a body passageway,and a second, expanded cross-sectional area. The expansion of themedical device body member can be accomplished in a variety of manners.Typically, the body member is expanded to its second cross-sectionalarea by a radially, outwardly extending force applied at least partiallyfrom the interior region of the body member (e.g. by use of a balloon,etc.); however, this is not required. When the second cross-sectionalarea is variable, the second cross-sectional area is typically dependentupon the amount of radially outward force applied to the body member.The medical device can be designed such that the body member expandswhile retaining the original length of the body member; however, this isnot required. The body member can have a first cross-sectional shapethat is generally circular so as to form a substantially tubular bodymember; however, the body member can have other cross-sectional shapes.When the medical device includes two or more body members, the two ormore body members can be connected together by at least one connectormember. The medical device can include rounded, smooth and/or bluntsurfaces to minimize and/or prevent damage to a body passageway as themedical device is inserted into a body passageway and/or expanded in abody passageway; however, this is not required. The medical device canbe treated with gamma, beta and/or e-beam radiation, and/or otherwisesterilized; however, this is not required. The medical device can havemultiple sections. The sections of the medical device can have a uniformarchitectural configuration, or can have differing architecturalconfigurations. Each of the sections of the medical device can be formedof a single part or formed of multiple parts which have been attached.When a section is formed of multiple parts, typically the section isformed into one continuous piece; however, this is not required. As canbe appreciated, the medical device can be formed into other devices suchas, but not limited to, an orthopedic device, PFO (patent foramen ovale)device, other types of grafts, guide wide, sheaths, stent catheters,electrophysiology catheters, other type of implant, valve, screw, nail,rod, hypotube, catheter, staple or cutting device, etc. The medicaldevice can include one or more surface structures and/ormicro-structures that include one or more biological agents, adhesivesand/or polymers; however, this is not required. These structures can beat least partially formed by MEMS (e.g., micro-machining, etc.)technology and/or other types oftechnology. The structures can bedesigned to contain and/or fluidly connected to a passageway thatincludes one or more biological agents; however, this is not required.These structures can be used to engage and/or penetrate surroundingtissue or organs once the medical device has been positioned on and/orin a patient; however, this is not required. One or more polymers,adhesives and/or biological agents can be inserted in these structuresand/or at least partially form these structures of the medical device;however, this is not required. The structures can be clustered togetheror disbursed throughout the surface of the medical device. Similarshaped and/or sized surface structures can be used, or different shapedand/or sized structures can be used. The surface topography of themedical device can be uniform or vary to achieve the desired operationand/or biological agent released from the medical device. As can beappreciated, the medical device or one or more regions of the medicaldevice can be constructed by use of one or more microelectromechanicalmanufacturing techniques (MEMS (e.g., micro-machining, etc.)); however,this is not required. Materials that can be used by MEMS (e.g.,micro-machining, etc.) technology include, but are not limited to,chitosan, a chitosan derivative, PLGA, a PLGA derivative, PLA, a PLAderivative, PEVA, a PEVA derivative, PBMA, a PBMA derivative, POE, a POEderivative, PGA, a PGA derivative, PLLA, a PLLA derivative, PAA, a PAAderivative, PEG, and chitosan, a chitosan derivative, PLGA, a PLGAderivative, PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA, a PBMAderivative, POE, a POE derivative, PGA, a PGA derivative, PLLA, a PLLAderivative, PAA, a PAA derivative, PEG, a PEG derivative, and/or a PEGderivative. The medical device is typically formed of a biocompatiblematerial. The amount of biological agent when used on the medicaldevice, can be selected for different medical treatments. Typically, theamount of biological agent used in a particular layer of biologicalagent or included in a polymer layer is about 0.01-100 ug per mm²;however, other amounts can be used. As can be appreciated, one or morebiological agents and/or polymers, when used, can be placed on differentregions of the medical device to achieve the desired operation and/orbiological agent release from the medical device. The medical device caninclude one or more coatings of biological agent on the other surface ofthe medical device to provide a burst of biological agent to aparticular site or region; however, this is not required. The one ormore biological agents, when used, can be selected so as to bechemically bonded to one or more polymers; however, this is notrequired. The time period the one or more biological agents, when used,are released from the medical device can vary. Generally, one or morebiological agents, when used, are released from the medical device forat least several days after the medical device is inserted in the bodyof a patient; however, this is not required. One or more biologicalagents, when used, can be released from the medical device for at leastabout one week after the medical device is inserted in the body of apatient, more typically, at least about two weeks after the medicaldevice is inserted in the body of a patient, and even more typically,about one week to one year after the medical device is inserted in thebody of a patient. As can be appreciated, the time frame that one ormore of the biological agents can be released from the medical devicecan be longer or shorter. One or more biological agents, when used, canbe released from the medical device controllably released and/ornon-controllably released. The time period for the release of two ormore biological agents from the medical device can be the same ordifferent. The type of the one or more biological agents used on themedical device, the release rate of the one or more biological agentsfrom the medical device, and/or the concentration of the one or morebiological agents being released from the medical device during acertain time period is typically selected to deliver one or morebiological agents directly to the area of disease after the medicaldevice has been implanted; however, this is not required. In onenon-limiting design of medical device, the medical device releases oneor more biological agents over a period of time after being inserted inthe body after the medical device has been implanted. In anothernon-limiting design of medical device, the medical device releases oneor more biological agents over a period of time after being inserted inthe body so that no further drug therapy is required about two weeks toone month after the medical device has been implanted. In yet anothernon-limiting design of medical device, the medical device releases oneor more biological agents over a period of up to one day after themedical device has been implanted. In still yet another non-limitingdesign of medical device, the medical device releases one or morebiological agents over a period of up to one week after the medicaldevice has been implanted. In a further non-limiting design of medicaldevice, the medical device releases one or more biological agents over aperiod of up to two weeks after the medical device has been implanted.In still a further non-limiting design of medical device, the medicaldevice releases one or more biological agents over a period of up to onemonth after the medical device has been implanted. In yet a furthernon-limiting design of medical device, the medical device releases oneor more biological agents over a period of up to one year after themedical device has been implanted. As can be appreciated, the time orrelease of one or more biological agents from the medical device can bemore than one year after the medical device has been implanted. The useof the medical device can be used in conjunction with other biologicalagents not on and/or in the medical device. For instance, the success ofthe medical device can be enhanced by infusing, injecting or consumingorally the same and/or different biological agent used for anti-plateletand/or anti-coagulation therapy that is being released from the medicaldevice. The introduction of biological agents from a source other thanthe medical device can have an additive or synergistic effect which canenhance the success of the medical device. Solid or liquid dosage formsof biological agents for oral administration can be used, and/or liquiddosage forms of biological agents for intravenous administration can beused. When solid dosage forms are used, such solid forms include, butare not limited to, capsules, tablets, effervescent tablets, chewabletablets, pills, powders, sachets, granules and gels. In such soliddosage forms, the biological agent can be admixed with at least onefiller material such as, but not limited to, sucrose, lactose or starch;however, this is not required. Such dosage forms can also includeadditional substances such as, but not limited to, inert diluents (e.g.,lubricating agents, etc.); however, this is not required. When capsules,tablets, effervescent tablets or pills are used, the dosage form canalso include buffering agents; however, this is not required. Softgelatin capsules can be prepared to contain a mixture of the biologicalagent in combination with vegetable oil or other types of oil; however,this is not required. Hard gelatin capsules can contain granules of thebiological agent in combination with a solid carrier such as, but notlimited to, lactose, potato starch, corn starch, cellulose derivativesof gelatin, etc; however, this is not required. Tablets and pills can beprepared with enteric coatings for additional time releasecharacteristics; however, this is not required. Liquid dosage forms ofthe biological agent for oral administration can includepharmaceutically acceptable emulsions, solutions, suspensions, syrups,elixirs, etc.; however, this is not required. Typically the introductionof one or more biological agents used for anti-platelet and/oranti-coagulation therapy from a source other than the medical device isabout one day after the medical device has been implanted in a patient,and typically up to about one week after the medical device has beenimplanted in a patient, and more typically up to about one month afterthe medical device has been implanted in a patient; however, it can beappreciated that periods of up to 2-3 months or more can be used.

One non-limiting object of the present invention is the provision of amedical device that is at least partially formed of a novel metal alloy.

Another and/or alternative non-limiting object of the present inventionis the provision of a medical device having improved procedural successrates.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is formed of amaterial that improves the physical properties of the medical device.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is at leastpartially formed of a novel metal alloy that has increased strength andcan also be used as a marker material.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that at least partiallyincludes a novel metal alloy that enables the medical device to beformed with less material without sacrificing the strength of themedical device as compared to prior medical devices.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is simple and costeffective to manufacture.

A further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is at leastpartially coated with one or more polymer coatings.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is coated with oneor more biological agents.

Yet a further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that has one or morepolymer coatings to at least partially control the release rate of oneor more biological agents.

Still yet a further and/or alternative non-limiting object of thepresent invention is the provision of a medical device that includes oneor more surface structures and/or micro-structures.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a method and process for forming a novelmetal alloy into a medical device.

Another and/or alternative non-limiting object of the present inventionis the provision of a medical device that includes one or more surfacestructures, micro-structures and/or internal structures and a protectivecoating that at least partially covers and/or protects such structures.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes one or moremarkers.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes and/or isused with one or more physical hindrances.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that can be used inconjunction with one or more biological agents not on or in the medicaldevice.

A further and/or alternative non-limiting object of the presentinvention is the provision of a method and process for forming a novelmetal alloy that inhibits or prevent the formation of micro-cracksduring the processing of the alloy into a medical device.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a method and process for forming a novelmetal alloy that inhibits or prevents in the introduction of impuritiesinto the alloy during the processing of the alloy into a medical device.

These and other advantages will become apparent to those skilled in theart upon the reading and following of this description taken togetherwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference may now be made to the drawings, which illustrate variousembodiments that the invention may take in physical form and in certainparts and arrangements of parts wherein:

FIG. 1 is a perspective view of a section of a medical device in theform of an unexpanded stent which permits delivery of the stent into abody passageway;

FIG. 2 is a cross-sectional view along line 2-2 of FIG. 1 illustratingthe novel metal alloy material that forms the medical device;

FIG. 3 is a cross-sectional view along line 2-2 of FIG. 1 illustratingthe novel metal alloy that forms the medical device that includes apolymer coating or biological agent;

FIG. 4 is a cross-sectional view along line 2-2 of FIG. 1 illustratingone type of coating on a medical device;

FIG. 5 is a cross-sectional view along line 2-2 of FIG. 1 illustratinganother type of coating on a medical device;

FIG. 6 is a cross-sectional view along line 2-2 of FIG. 1 illustratinganother type of coating on a medical device;

FIG. 7 is a cross-sectional view along line 2-2 of FIG. 1 illustratinganother type of coating on a medical device;

FIGS. 8 and 9 are a cross-sectional view along line 2-2 of FIG. 1illustrating the novel metal alloy that includes one or moremicro-needles on the surface of the novel metal alloy;

FIG. 10 is a cross-sectional view along line 2-2 of FIG. 1 illustratingthe novel metal alloy that includes a plurality of micro-needles on thesurface of the novel metal alloy which are formed of one or morepolymers and biological agents;

FIG. 11 is a cross-sectional view along line 2-2 of FIG. 1 illustratingthe novel metal alloy that includes one or more micro-structures on thesurface of the novel metal alloy;

FIG. 12 is a cross-sectional view along line 2-2 of FIG. 1 illustratingone or more micro-needles on the surface of the novel metal alloy whichone or more micro-needles are formed from one or more polymers and/orbiological agents and are coated with one or more polymers and/orbiological agents;

FIG. 13 is a cross-sectional view along line 2-2 of FIG. 1 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent;

FIG. 14 is a cross-sectional view along line 2-2 of FIG. 1 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and polymer;

FIG. 15 is a cross-sectional view along line 2-2 of FIG. 1 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and coated with a polymer;

FIG. 16 is a cross-sectional view along line 2-2 of FIG. 1 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and polymer and coated with a polymer;

FIG. 17 is a cross-sectional view along line 2-2 of FIG. 1 illustratingmicro-needles on the surface of the medical device that are formed of apolymer and includes an internal cavity that includes a biologicalagent;

FIG. 18 is a cross-sectional view of a micro-needle that is penetratinginto the inner surface of a body passageway or organ; and,

FIG. 19 is one non-limiting process in accordance with the invention formanufacturing a stent from a molybdenum and rhenium alloy.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the drawings wherein the showings are for the purposeof illustrating embodiments of the invention only and not for thepurpose of limiting the same, FIGS. 1-18 disclose a medical device inthe form of a stent for use in a body passageway. The stent isparticularly useful in the cardiovascular field; however, the stent canbe used in other medical fields such as, but not limited to, orthopedicfield, cardiology field, pulmonology field, urology field, nephrologyfield, gastroenterology field, gynecology field, otolaryngology field orother surgical fields. Additionally or alternatively, the medical deviceis not limited to a stent, thus can be in the form of many other medicaldevices (e.g., a staple, an orthopedic implant, a valve, a vascularimplant, a pacemaker, a spinal implant, a guide wire, nail, rod, screw,etc.).

The stent, when used for vascular applications, can be used to addressvarious medical problems such as, but not limited to, restenosis,atherosclerosis, atherogenesis, angina, ischemic disease, congestiveheart failure or pulmonary edema associated with acute myocardialinfarction, atherosclerosis, thrombosis, controlling blood pressure inhypertension, platelet adhesion, platelet aggregation, smooth musclecell proliferation, vascular complications, wounds, myocardialinfarction, pulmonary thromboembolism, cerebral thromboembolism,thrombophlebitis, thrombocytopenia or bleeding disorders.

As illustrated in FIG. 1, stent 20 is in the form of an expandable stentthat includes at least one tubular shaped body member 30 having a firstend 32, a second end 34, and member structures 36 disposed between thefirst and second ends. As can be appreciated, the stent can be formed ofa plurality of body members connected together. Body member 30 has afirst diameter which permits delivery of the body member into a bodypassageway. The first diameter of the body member is illustrated assubstantially constant along the longitudinal length of the body member.As can be appreciated, the body member can have a varying first diameteralong at least a portion of the longitudinal length of the body member.The body member also has a second expanded diameter, not shown. Thesecond diameter typically varies in size; however, the second diametercan be non-variable in size. The stent can be expanded in a variety ofways such as by a balloon. A balloon expandable stent is typicallypre-mounted or crimped onto an angioplasty balloon catheter. A ballooncatheter is then positioned into the patient via a guide wire. Once thestent is properly positioned, the balloon catheter is inflated to theappropriate pressure for stent expansion. After the stent has beenexpanded, the balloon catheter is deflated and withdrawn, leaving thestent deployed at the treatment area. One or more surfaces of the stentcan be treated so as to have generally smooth surfaces; however, this isnot required. Generally, one or more ends of the stent are treated byfiling, buffing, polishing, grinding, coating, and/or the like to removeor reduce the number of rough and/or sharp surfaces; however, this isnot required. The smooth surfaces of the ends reduce potential damage tosurrounding tissue as the stent is positioned in and/or expanded in abody passageway.

The stent as illustrated in FIG. 1 is typically designed to be insertedinto a diseased area in a body passageway and to expand the diseasedarea to enable better or proper fluid flow through the body passageway;however, the stent can be used for other or additional reasons. In onespecific non-limiting example, the stent can be used to open anobstructed blood vessel. The stent can include and/or be used with oneor more biological agents used to inhibit thrombosis, in-stentrestenosis, vascular narrowing and/or restenosis after the stent hasbeen inserted into the blood vessel; however, this is not required. Theone or more biological agents, when used, can also or alternatively beused to remove and/or dissolve lipids, fibroblast, fibrin, etc. from theblood vessel so as to at least partially clean the blood vessel of suchsubstances in the region of the stent and/or down stream of the stent.As can be appreciated, the one or more biological agents, when used, canhave additional or other functions.

The novel metal alloy that at least partially forms the medical deviceincludes a majority of Mo and Re. The novel metal alloy has improvedphysical properties. The novel metal alloy used to at least partiallyform the medical device improves one or more properties (e.g., strength,durability, hardness, biostability, bendability, coefficient offriction, radial strength, flexibility, tensile strength; elongation,longitudinal lengthening, stress-strain properties, improved recoilproperties, radiopacity, heat sensitivity, biocapatability, etc.) ofsuch medical devices. In some instances, the use of the novel metalalloy can reduce the volume, bulk and/or weight as compared to priormedical devices made from traditional materials; however, this is notrequired. The one or more materials used to form the medical deviceinclude one or more properties selected to form a medical device whichpromotes the success of the medical device.

The novel metal alloy that at least partially forms the stent includes amajority weight percent of Mo and Re. The novel metal alloy typicallyforms at least a majority weight percent of the stent; however, this isnot required. As illustrated in FIG. 1, the member structures 36 ofstent 20 are formed of 98-100% of the novel metal alloy 40. In onenon-limiting novel metal alloy composition, the metal alloy includesabout 44-48 weight percent Re and about 52-56 weight percent Mo. In onenon-limiting example, the novel metal alloy is a solid solution thatincludes about 44.5-47.5 weight percent Re and 52.5-55.5 weight percentMo, a weight percent of Re plus Mo of at least about 99.9%, less thanabout 50 ppm carbon, less than about 10 ppm oxygen, less than about 20ppm nitrogen, a carbon to oxygen atomic ratio of about 2.5-10:1, and nomore than about 0.1 weight impurities. In another non-limiting novelmetal alloy composition, the metal alloy includes about 44-48 weightpercent Re, about 52-56 weight percent Mo, and up to about 0.5 weightpercent Ti, Y and/or Zr. In one non-limiting example, the novel metalalloy is a solid solution that includes about 44.5-47.5 weight percentRe, 52.5-55.5 weight percent Mo, a weight percent of Mo plus Re plus Ti,Y and/or Zr that is at least about 99.9%, 0.3-0.4 weight percent Ti,0.06-0.1 weight percent Zr, 0-0.05 weight percent Y, a weight ratio ofTi:Zr of 1-3:1, less than about 50 ppm carbon, less than about 10 ppmoxygen, less than about 20 ppm nitrogen, a carbon to oxygen atomic ratioof about 2.5-10:1, and no more than about 0.1 weight impurities. Thetensile elongation of the novel metal alloy is about 25-35%, the averagedensity of the novel metal alloy is at least about 13.4 gm/cc., theaverage yield strength of the novel metal alloy is about at least about98 (ksi), the average ultimate tensile strength of the novel metal alloyis about 100-150 UTS (ksi), and the average hardness of the novel metalalloy is about 80-100 (HRC) at 77° F. The 99.9 weight percent purity ofthe metal alloy forms a solid or homogenous solution. The uniquecombination of carbon and oxygen redistributes the oxygen at the grainboundary of the metal alloy, which in turn helps in reducingmicrocracks(defects) in the ultimately formed stent. A controlled carbonto oxygen atomic ratio can also be used to obtain a high ductility ofthe metal alloy which can be measured in part as tensile elongation. Anincrease in tensile elongation is an important attribute when formingthe metal alloy into the stent. The purity of the metal alloy alsoresults in a substantially uniform density throughout the metal alloy.The density of the solid homogeneous solution of the metal alloy resultsin the high radiopacity of the metal alloy. The addition of rhenium inthe metal alloy improves the ductility of the molybdenum. The additionof titanium, yttrium and/or zirconium, when used, facilitates in grainsize reduction of the novel metal alloy, improves ductility of the novelmetal alloy and/or increases the yield strength of the novel metalalloy. The solid or homogeneous solution of the novel metal alloyresults in a novel metal alloy having the desired tensile yield strengthand ultimate tensile strength of the novel metal alloy. Nitrogen in thenovel metal alloy is an interstitial element that raises the DuctileBrittle Transition Temperature (DBTT). When the DBTT is too high, thenovel metal alloy can become brittle. The maintenance of nitrogen belowabout 20 ppm overcomes this brittleness problem. The combination ofthese various properties of the solid or homogeneous solution of thenovel metal alloy enables the novel metal alloy to be formed into astent that has superior performance characteristics such as, but notlimited tom high radiopacity with thinner and narrower struts andsimultaneously having a radial force adequate to retain the vessel lumenfairly open and prevent any recoil. The novel metal alloy can befabricated from a tubing with an outer diameter as small as about 0.070inch and with a wall thickness as small as about 0.002 inch. In oneparticular design, the average wall thickness after the final processingof the alloytube is about 0.0021-0.00362 inch, and the averageconcentricity deviation after the final processing of the alloy tube isabout 1-20%. As can be appreciated, the size values of the processedalloy rod set forth above are merely exemplary for using the novel metalalloy to form a stent for use in the vascular system of a patient. Whenthe novel metal alloy is used to form other types of stents for use indifferent regions of a body, the size values of the final processednovel metal alloy can be different. The solid or homogeneous solution ofthe novel metal alloy has the unique characteristics of purity,ductility, grain size, tensile elongation, yield strength, and tensilestrength that permits the novel metal alloy to be fabricated into thestent tubing without creating microcracks that are detrimental to thestent properties.

Referring again to FIGS. 1-2, the stent is an expandable stent that canbe used to at least partially expand occluded segments of a bodypassageway; however, the stent can have other or additional uses. Forexample, the expandable stent can be used as, but not limited to, 1) asupportive stent placement within a blocked vasculature opened bytransluminal recanalization, which are likely to collapse in the absenceof an internal support; 2) forming a catheter passage throughmediastinal and/or other veins occluded by inoperable cancers; 3)reinforcing a catheter creating intrahepatic communication betweenportal and/or hepatic veins in patients suffering from portalhypertension; 4) a supportive stent placement of narrowing of theesophagus, the intestine, the ureter and/or the urethra; and/or 5) asupportive stent reinforcement of reopened and previously obstructedbile ducts. Accordingly, use of the term “stent” encompasses theforegoing or other usages within various types of body passageways, andalso encompasses use for expanding a body passageway. The stent can beimplanted or applied in a body passageway by techniques such as, but notlimited to, balloon delivery, sheath catheter delivery, etc.

The novel metal alloy can be formed into a stent by a variety ofmanufacturing processes. One non-limiting process for forming the stentas illustrated in FIG. 19. As illustrated in this non-limiting process,the first step to form a stent is to form a tube of a solid solution ofmolybdenum and rhenium alloy. The tube can be form in a variety of ways.Process step 700 illustrates that metal powders of molybdenum andrhenium are selected to form the tube. The powders of molybdenum andrhenium constitute a majority weight percent of the materials used toform the metal tube. Small amounts of an additional metal such astitanium, yttrium and/or zirconium can also be used; however, this isnot required. The purity of the metal powders is selected to minimizethe carbon, oxygen and nitrogen content in the metal powder. Typicallythe carbon content of the metal powders is less than about 150 ppm, theoxygen content of the metal powders is less than about 100 ppm and thenitrogen content of the metal powders is less than about 40 ppm.

After the metal powders have been selected, the metal powders aresubstantially homogeneously mixed together as illustrated in processstep 710. After the metal powders are mixed together, the metal powdersare isostatically consolidated to form a tube. One non-limitingisostatic consolidation process is a cold isostatic pressing (CIP)process. The isostatic consolidation process typically occurs in avacuum environment, an oxygen reducing environment, or in an inertatmosphere. The average density of the metal tube obtained by theisostatic consolidation process is about 80-90% of the final averagedensity of the tube. One non-limiting composition of the tube is a solidsolution of about 44-48 weight percent rhenium, about 52-56 weightpercent molybdenum, up to about 0.5 weight percent Ti, Y and/or Zr, andno more than about 0.1 weight impurities. After the metal powder hasbeen pressed together, the metal power is sintered to fuse the metalpowders together and to form the tube of novel metal alloy asillustrated in step 720. The sinter of the metal powders occurs at atemperature of about 2000-2500° C. for about 5-120 minutes; however,other temperatures and/or sintering time can be used. The sintering ofthe metal powder typically takes place in an oxygen reducing environmentto inhibit or prevent impurities from becoming embedded in the novelmetal alloy and/or to further reduce the amount of carbon and/or oxygenin the formed tube. After the sintering process, the tube is formed of asolid solution of the novel metal alloy and has an as-sintered averagedensity of about 90-99% the minimum theoretical density of the novelmetal alloy. Typically, the sintered tube has a final average density ofabout 13-14 gm/cc. The length of the formed tube is typically about 48inches or less; however, longer lengths can be formed. The averageconcentricity deviation of the tube is typically about 1-18%. In onenon-limiting tube configuration, the tube has an inner diameter of about0.31 inch plus or minus about 0.002 inch and an outer diameter of about0.5 inch plus or minus about 0.002 inch. The wall thickness of the tubeis about 0.095 inch plus or minus about 0.002 inch. As can beappreciated, this is just one example of many different sized tubes thatcan be formed.

The tube can be cleaned after the tube has been form sintered; however,this is not required. The cleaning of the tube is used to removeimpurities and/or contaminants from the surfaces of the tube. Impuritiesand contaminants (e.g., carbon, oxygen, etc.) can become incorporatedinto the novel metal alloy during the processing of the tube. Theinclusion of impurities and contaminants in the novel metal alloy canresult in premature micro-cracking of the novel metal alloy and/or theadverse affect on one or more physical properties of the novel metalalloy. The cleaning of the tube can be accomplished by a variety oftechniques such as, but not limited to, 1) using a solvent (e.g.acetone, methyl alcohol, etc.) and wiping the novel metal alloy with aKimwipe or other appropriate towel, and/or 2) by at least partiallydipping or immersing the novel metal alloy in a solvent and thenultrasonically cleaning the novel metal alloy. As can be appreciated,the tube can be cleaned in other or additional ways.

After the tube has been sintered, and optionally cleaned, the tube isthen drawn through a die one or more times to reduce the inner and outerdiameter of the tube and the wall thickness of the tube to the desiredsize. As illustrated in process step 730, the tube is reduced in size bythe use of a plug drawing process. During the plug drawing process, thetube is heated (i.e., up to about 300° C.) and protected in a vacuumenvironment, an oxygen reducing environment, or inert environment. Onenon-limiting oxygen reducing environment includes argon and about 1-10volume percent hydrogen. The amount of outer diameter draw down of thetube each time the tube is plug drawn is typically no more than about10%. Controlling the degree of draw down facilitates in preventing theformation of micro-cracks during the drawing process. After each drawingprocess, the tube can be cleaned as illustrated in step 740; however,this is not required.

Prior to the tube being drawn down more than about 35-45% from itsoriginal outer diameter after the sintering process, the tube isannealed as illustrated in process step 750. If the tube is to befurther drawn down after being initially annealed, a subsequentannealing process should be completed prior to the outer diameter of thetube being drawn down more than about 35-45% since a previous annealingprocess. As such, the tube should also be annealed at least once priorto the tube outer diameter being drawn down more than about 35-45% sincebeing originally sintered or being previously annealed. This controlledannealing facilitates in preventing the formation of micro-cracks duringthe drawing process. The annealing process of the tube typically takesplace in a vacuum environment, an inert atmosphere, or an oxygenreducing environment (e.g., argon, argon and 1-10% hydrogen, etc.) at atemperature of about 1400-1500° C. for a period of about 5-30 minutes;however, other temperatures and/or times can be used. The use of anoxygen reducing environment during the annealing process can be used toreduce the amount of oxygen in the tube. The chamber in which the tubeis annealed should be substantially free of impurities such as, but notlimited to, carbon, oxygen, and/or nitrogen. The annealing chambertypically is formed of a material that will not impart impurities to thetube as the tube is being annealed. One non-limiting material that canbe used to form the annealing chamber is a molybdenum TZM alloy.

Prior to each annealing process, the tube is cleaned and/or pickled toremove oxides and/or other impurities from the surface of the tube asillustrated in process step 740. Typically the tube is cleaned by firstusing a solvent (e.g. acetone, methyl alcohol, etc.) and wiping thenovel metal alloy with a Kimwipe or other appropriate towel, and/or byat least partially dipping or immersing the tube in a solvent and thenultrasonically cleaning the novel metal alloy. As can be appreciated,the tube can be cleaned in other and/or additional ways. After the tubehas been cleaned by use of a solvent, the tube is typically furthercleaned by use of a pickling process. The pickling process includes theuse of one or more acids to remove impurities from the surface of thetube. Non-limiting examples of acids that can be used as the picklingsolution include, but are not limited to, nitric acid, acetic acid,sulfuric acid, hydrochloric acid, and/or hydrofluoric acid. The acidsolution and acid concentration and time of pickling are selected toremove oxides and other impurities on the tube surface without damagingor over etching the surface of the tube. During the pickling process,the tube is fully or partially immersed in the pickling solution for asufficient amount of time to remove the impurities from the surface ofthe tube. After the tube has been pickled, the tube is typically rinsedwith a solvent (e.g., acetone, methyl alcohol, etc.) to remove anypickling solution from the tube and then the tube is allowed to dry. Thecleaning of the tube prior to the tube being annealed removes impuritiesand/or other materials from the surfaces of the tube that could becomepermanently embedded into the tubing during the annealing processes.These imbedded impurities could adversely affect the physical propertiesof the novel metal alloy as the tube is formed into a medical device,and/or can adversely affect the operation and/or life of the medicaldevice. As can be appreciated, the tube can be again cleaned and/orpickled after being annealed and prior to being drawn down in the plugdrawing process; however, this is not required.

Process steps 730-750 can be repeated as necessary until the tube isdrawn down to the desired size. In one non-limiting process, a tube thatis originally formed after being sintered has an inner diameter of about0.31 inch plus or minus about 0.002 inch, an outer diameter of about 0.5inch plus or minus about 0.002 inch, and a wall thickness of about 0.095inch plus or minus about 0.002 inch. After the tube has been fully drawndown, the tube has an outer diameter of about 0.070 inch, a wallthickness of about 0.0021-0.00362 inch, and the average concentricitydeviation of less than about 10%. Such small sizes for stents which canbe successfully used in a vascular system have heretofore not beenpossible when formed by other types of metal alloys. Typically, the wallthickness of stent had to be at least about 0.0027-0.003 inch, or thestent would not have sufficient radial force to maintain the stent in anexpanded state after being expanded. The novel metal alloy of thepresent invention is believed to be able to have a wall thickness of assmall as about 0.0015 inch and still have sufficient radial force tomaintain a stent in an expanded state after being expanded. As such,when a tube is formed into a stent, the wall thickness of the tube canbe drawn down to less than about 0.0027 inch to form a stent. As can beappreciated, this is just one example of many different sized tubes thatcan be formed by the process of the present invention.

Once the tube has been drawn down to its final size, the tube istypically cleaned (Process Step 740), annealed (Process Step 750) andthen again cleaned (Process Step 760). The cleaning step of process step760 can include merely solvent cleaning, or can also include pickling.

After the tube has been cleaned in process step 760, the tube is thencut into the form of a stent as illustrated in FIG. 19. As can beappreciated, other stent designs can be formed during the cuttingprocess as set forth in process step 770. The cutting of the tube istypically conducted by a laser. The laser that is used to cut the tubeis selected so that the beam strength used to heat the tube can obtain acutting temperature of at least about 2350° C. Non-limiting examples oflasers that can be used include a pulsed YAG-ND or CO₂ laser. Thecutting of the tube by the laser occurs in an oxygen reducingenvironment such as an argon and 1-10 percent by volume hydrogenenvironment; however, a vacuum environment, an inert environment, oranother type of oxygen reducing environment can be used. During thecutting of the tube, the tube is typically stabilized so as to inhibitor prevent vibration of the tube during the cutting process, whichvibrations can result in the formation of micro-cracks in the tube asthe tube is cut. The tube is typically stabilized by an apparatus formedof molybdenum, rhenium, tungsten, molybdenum TZM alloy, ceramic, etc. soas to not introduce contaminates to the tube during the cutting process;however, this is not required. The average amplitude of vibration duringthe cutting of the tube is typically no more than about 50% the wallthickness of the tube. As such, for a tube having a wall thickness ofabout 0.0024 inch, the average amplitude of vibration of the tube duringthe cutting process is no more than about 0.0012 inch.

The formed stent typically has a tensile elongation of about 25-35%, anaverage density of about 13.4-14 gm/cc., an average yield strength of atleast about 100 (ksi), an average ultimate tensile strength of about100-150 UTS (ksi), and an average hardness of about 80-100 (HRC) at 77°F. The solid or homogeneous solution of the metal alloy that is used toform the stent has the unique characteristics of purity, ductility,grain size, tensile elongation, yield strength and ultimate tensilestrength that permits 1) the metal alloy to be fabricated into the stentfrom the tube without creating microcracks which are detrimental to thestent properties, and 2) the manufacture of a stent that has improvedphysical properties over stents formed from different materials.

After the stent has been cut, the stent can be further processed;however, this is not required. The one or more processes can include,but are not limited to, 1) electropolishing the stent, 2) treating oneor more surfaces of the stent to create generally smooth surfaces (e.g.,filing, buffing, polishing, grinding, coating, etc.), 3) at leastpartially coating the stent with one or more biological agents, 4) atleast partially coating the stent with one or more polymers, 5) formingone or more surface structures and/or micro-structures on one or moreportions of the stent, and/or 6) inserting one or more markers on one ormore portions of the stent.

The stent can include one or more coating and/or one or more surfacestructures and/or micro-structures as illustrated in FIGS. 3-18. The oneor more surface structures and/or micro-structures can be formed by avariety of processes (e.g., machining, chemical modifications, chemicalreactions, MEMS (e.g., micro-machining, etc.), etching, laser cutting,etc.). The one or more coatings and/or one or more surface structuresand/or micro-structures of the stent can be used for a variety ofpurposes such as, but not limited to, 1) increasing the bonding and/oradhesion of one or more biological agents, adhesives, marker materialsand/or polymers to the stent, 2) changing the appearance or surfacecharacteristics of the stent, and/or 3) controlling the release rate ofone or more biological agents.

As illustrated in FIG. 3, the novel metal alloy 40 that form the body ofstent 20 can be coated with one or more biological agents or polymers 50that can be used to improve the functionality or success of the stent.The one or more polymer coatings can be porous or non-porous polymers.Non-limiting examples of the one or more polymers that can be coated onone or more regions of the novel metal alloy 40 include, but are notlimited to, parylene, a parylene derivative, chitosan, a chitosanderivative, PLGA, a PLGA derivative, PLA, a PLA derivative, PEVA, a PEVAderivative, PBMA, a PBMA derivative, POE, a POE derivative, PGA, a PGAderivative, PLLA, a PLLA derivative, PAA, a PAA derivative, PEG, a PEGderivative, or combinations thereof. The one or more biological agentscan include, but are not limited to, anti-biotic agents, anti-bodytargeted therapy agents, anti-hypertensive agents, anti-microbialagents, anti-mitotic agents, anti-oxidants, anti-polymerases agents,anti-proliferative agents, anti-secretory agents, anti-tumor agents,anti-viral agents, bioactive agents, chemotherapeutic agents, cellularcomponents, cytoskeletal inhibitors, drug, growth factors, growth factorantagonists, hormones, immunosuppressive agents, living cells,non-steroidal anti-inflammatory drugs, radioactive materials,radio-therapeutic agents, thrombolytic agents, vasodilator agents, etc.Non-limiting examples of biological agents that can be used include avascular active agent that inhibits and/or prevents restenosis, vascularnarrowing and/or in-stent restenosis such as, but not limited to,trapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. As canbe appreciated, other or additional biological agents can be included onthe stent to improve the functionality or success of the stent. Theamount of biological agent delivered to a certain region of a patient'sbody can be controlled by varying the type of biological agent, thecoating thickness of the biological agent, the drug concentration of thebiological agent, the solubility of the biological agent, the locationthe biological agent that is coated and/or impregnated on and/in thestent, the amount of surface area of the stent that is coated and/orimpregnated with the biological agent, the location of the biologicalagent on the stent, etc.

When one or more biological agents are included on and/or in the stent,the one or more biological agents can be controllably released and/orimmediately released to optimize their effects and/or to compliment thefunction and success of the stent. The controlled release can beaccomplished by 1) controlling the size of the surface structures,micro-structures and/or internal structures in the stent, and/or 2)using one or more polymer coatings; however, other or additionalmechanisms can be used to control the release rate of one or morebiological agents from the stent. The controlled release can beaccomplished by 1) controlling the size of the surface structures,micro-structures and/or internal structures in the stent, and/or 2)using one or more polymer coatings; however, other or additionalmechanisms can be used to control the release rate of one or morebiological agents from the stent. For example, the amount of biologicalagent delivered to a certain region of a patient's body can becontrolled by, but not limited to, one or more of the following: a)selecting the type of biological agent to be used on and/or in thestent, b) selecting the amount of biological agent to be used on and/orin the stent, c) selecting the coating thickness of the biological agentto be used on the stent, d) selecting the drug concentration of thebiological agent to be used on and/or in the stent, e) selecting thesolubility of the biological agent to be used on and/or in the stent, f)selecting the location the biological agent that is to be coated and/orimpregnated on and/in the stent, g) selecting the amount of surface areaof the stent that is coated and/or impregnated with the biologicalagent, h) selecting the location of the biological agent on the stent,i) selecting the size, shape, amount and/or location of the one or moresurface structures, micro-structures and/or internal structures of thestent that include and/or are integrated with the biological agent, j)selecting the type and/or amount of polymer to be mixed with thebiological agent, k) selecting the type, amount and/or coating thicknessof the polymer coating used to at least partially coat and/orencapsulate the biological agent, etc. The one or more biological agentscan be combined with and/or at least partially coated with a polymerthat affects the rate at which the biological agent is released from thestent; however, this is not required. The polymer coating can also oralternatively be used to assist in binding the one or more biologicalagents to the stent; however, this is not required. The polymer coating,when used, can be biodegradable or biostable. The polymer coating can beformulated to form a bond with the biological agent to the stent;however, this is not required. The one or more polymers used in thepolymer coating and the one or more biological agents can be mixedtogether prior to being applied to the stent; however, this is notrequired. The one or more biological agents that are used in combinationwith a one or more polymers in the polymer coating can control therelease of the biological agent by molecular diffusion; however, this isnot required. The thickness of the polymer coating can be about 0.5-25μ;however, other coating thickness can be used. The time period the one ormore biological agents are released from the stent can vary. The one ormore biological agents, when used, can be coated on the surface of thenovel metal alloy, on the surface of one or more polymer layers, and/ormixed with one or more polymer layers. One or more biological agents canalso be coated on the top surface of stent 20. At least one biologicalagent can be entrapped within and/or coated over with a non-porouspolymer layer to at least partially control the release rate of thebiological rate; however, this is not required. When a non-porouspolymer layer is used on the stent, the non-porous polymer typicallyincludes parylene C, parylene N, parylene F and/or a parylenederivative; however, other or additional polymers can be used. Variouscoating combinations can be used on the stent. For instance, a polymerlayer that includes one or more polymers can be coated on the top of thelayer of one or more biological agents; however, this is not required.In another example, the novel metal alloy 40 can includes a layer of oneor more polymers. A layer of one or more biological agent can be coatedon the top of the layer of one or more polymers; however, this is notrequired. Furthermore, one or more polymers can be coated on the layerof one or more biological agents; however, this is not required. As canbe appreciated other coating combinations can be used. Generally, one ormore biological agent are released from the stent for at least severaldays after the stent is inserted in the body of a patient; however, thisis not required. Generally, one or more biological agents are releasedfrom the stent for at least about 1-7 days after the stent is insertedin the body of a patient, typically at least about 1-14 days after thestent is inserted in the body of a patient, and more typically about1-365 days after the stent is inserted in the body of a patient;however, this is not required. As can be appreciated, the time framethat one or more of the biological agents are released from the stentcan be shorter or longer. The one or more biological agents that arereleased from the stent can be controllably released and/ornon-controllably released. The time period for the release of two ormore biological agents from the stent can be the same or different. Thetype of the one or more biological agents used on the stent, the releaserate of the one or more biological agents from the stent, and/or theconcentration of the one or more biological agents being released fromthe stent during a certain time period is typically selected to deliverthe one or more biological agents to the area of treatment and/ordisease. When the stent is used in the vascular system, the one or morebiological agent can be used to inhibit or prevent thrombosis,restenosis, vascular narrowing and/or in-stent restenosis after thestent has been implanted; however, this is not required. When the stentis use in the vascular system, the biological agent that is generallyincluded on and/or in the stent is, but not limited to, trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof;however, it will be appreciated that other or additional biologicalagents can be used. In addition, many other or additional biologicalagents can be included on and/or in the stent such as, but not limitedto, the following categories of biological agents: thrombolytics,vasodilators, anti-hypertensive agents, anti-microbial or anti-biotic,anti-mitotic, anti-proliferative, anti-secretory agents, non-steroidalanti-inflammatory drugs, immunosuppressive agents, growth factors andgrowth factor antagonists, chemotherapeutic agents, anti-polymerases,anti-viral agents, anti-body targeted therapy agents, hormones,anti-oxidants, radio-therapeutic agents, radiopaque agents and/orradio-labeled agents.

The surface of the novel metal alloy 40 can be treated to enhance thecoating of the stent and/or to enhance the mechanical characteristics ofthe stent; however, this is not required. Such surface treatmenttechniques include, but are not limited to, cleaning, buffing,smoothing, etching (chemical etching, plasma etching, etc.), etc. Whenan etching process is used, various gasses can be used for such asurface treatment process such as, but not limited to, carbon dioxide,nitrogen, oxygen, Freon, helium, hydrogen, etc. The plasma etchingprocess can be used to clean the surface of the stent, change thesurface properties of the stent so as to affect the adhesion properties,lubricity properties, etc. of the surface of the stent. As can beappreciated, other or additional surface treatment processes can be usedprior to the coating of one or more biological agents and/or polymers onthe surface of the stent.

As illustrated in FIGS. 3-7, various coating combinations can be used onthe stent. As indicated above with reference to FIG. 3, the basestructure 40 of the stent includes a layer 50 of biological agent and/orpolymer. The layer of biological agent and/or polymer can include one ormore biological agents and/or polymers. In one non-limiting example,layer 50 includes one or more biological agents that include trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. In onenon-limiting example, layer 50 includes one or more polymers. Thepolymer layer can include one or more polymers. The polymer layer caninclude one or more porous polymers and/or non-porous polymers, and/orbiostable and/or biodegradable polymers. When the stent includes and/oris coated with one or more polymers, such polymers can include, but arenot limited to, parylene, parylene C, parylene N, parylene F, PLGA,PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivativesof one or more of these polymers. The polymer layer, when including oneor more non-porous polymers, at least partially controls a rate ofrelease by molecular diffusion of the one or more biological agents inlayer 50. The one or more non-porous polymers can include, but are notlimited to, parylene C, parylene N, parylene F and/or a parylenederivative.

As illustrated in FIG. 4, the base structure 40 of the stent 20 includesa layer 52 of biological agent. The layer of biological agent caninclude one or more biological agents. In one non-limiting example, thebiological agent includes trapidil, trapidil derivatives, taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. A polymer layer 60 is coated onthe top of layer 52. The polymer layer can include one or more polymers.The polymer layer can include one or more porous polymers and/ornon-porous polymers, and/or one or more biostable and/or biodegradablepolymers. Non-limiting examples of one or more polymers that can be usedinclude, but are not limited to, parylene, parylene C, parylene N,parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosanand/or derivatives of one or more of these polymers. In one non-limitingexample, the polymer layer includes one or more non-porous polymers toat least partially control a rate of release by molecular diffusion ofthe one or more biological agents of layer 52 from stent 20. The one ormore non-porous polymers can include, but is not limited to, parylene C,parylene N, parylene F and/or a parylene derivative.

As illustrated in FIG. 5, the base structure 40 of stent 20 includes alayer 70 of polymer and biological agent. Layer 70 can include one ormore biological agents mixed with one or more polymers. In onenon-limiting example, the one or more biological agents includetrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Theone or more polymers can include one or more porous and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers included in layer 70 include anon-porous polymer to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 70.The non-porous polymer can include, but is not limited to, parylene C,parylene N, parylene F and/or a parylene derivative.

As illustrated in FIG. 6, the base structure 40 of stent 20 includes alayer 80 of polymer. Layer 80 can include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. The one ormore non-porous polymers, when used, can include, but are not limitedto, parylene C, parylene N, parylene F and/or a parylene derivative. Alayer 90 of one or more biological agents is coated on top of polymerlayer 80. Polymer layer 80 can be used to facilitate in the securing oflayer 90 to the stent; however, this is not required. In onenon-limiting example, the one or more biological agents includetrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Theplacement of a layer of biological agent on the top surface of the stentcan provide a burst of biological agent in the treatment area (e.g.,body passageway, etc.) after insertion of the stent. In one non-limitingexample, the one or more biological agents include trapidil and/orderivatives thereof.

As illustrated in FIG. 7, the base structure 40 of stent 20 includes alayer 100 of one or more biological agents. In one non-limiting example,the one or more biological agents include trapidil, trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. A polymer layer 110is coated on the top of layer 100. The polymer layer can include one ormore polymers. The polymer layer can include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. In onenon-limiting example, the polymer layer includes one or more non-porouspolymers to at least partially control a rate of release by moleculardiffusion of the one or more biological agents of layer 100 from stent20. The one or more non-porous polymers can include, but are not limitedto, parylene C, parylene N, parylene F and/or a parylene derivative. Alayer 120 of biological agent is coated on top of polymer layer 110.Layer 120 can include one or more biological agents. In one non-limitingexample, the one or more biological agents include trapidil, trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. The placement of alayer of biological agent on the top surface of the stent provide canprovide a burst of one or more biological agents in the treatment area(e.g., body passageway, etc.) after insertion of the stent. In onenon-limiting example, the one or more biological agents includetrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. As canbe appreciated, other combinations of polymer layer and layer ofbiological agent can be used on the stent. These other combinations arealso encompassed within the scope of the present invention.

Referring now to FIGS. 8-10, the novel metal alloy 40 of stent 20includes one or more needles or micro-needles 200, 210, 220 formed onthe surface of the novel metal alloy. These needles or micro-needles canbe formed by MEMS (e.g., micro-machining, etc.) technology and/or byother processes. As illustrated in FIGS. 8-10, the needles ormicro-needles can have a variety of shapes and sizes. The needles ormicro-needles can be at least partially formed from one or more polymersand/or biological agents. It can be appreciated that the needles ormicro-needles can be at least partially formed of other of additionalmaterial such as, but not limited to one or more adhesives, etc. Asillustrated in FIG. 10, the needles or micro-needles include acombination of one or more polymers 232 and/or one or more biologicalagents 230. As can be appreciated, one or more layer of one or morebiological agents and/or polymers can be coated on the needles ormicro-needles; however, this is not required. When the one or moreneedles or micro-needles include and/or are coated with one or morebiological agents, such biological agents can include, but are notlimited to, trapidil, trapidil derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof; however other or additional biological agents canbe used. The use of one or more biological agents to coat the topsurface of the needles or micro-needles can provide a burst ofbiological agent in the interior of the blood vessel and/or the bloodvessel itself during and/or after insertion of the stent.

Referring now to FIG. 11, the novel metal alloy 40 of stent 20 includesone or more surface structures or micro-structures 240 in the form of amound; however, it can be appreciated that other or additional shapescan be used. The mound is formed on the surface of the novel metalalloy. The mound can be formed by MEMS (e.g., micro-machining, etc.)technology and/or by other processes. The mound is shown to be formed ofone or more biological agents; however, it can be appreciated that themound can be formed of one or more polymers or a combination of one ormore polymers and biological agents. As can also be appreciated, otheror additional materials can be used to at least partially form themound. The one or more biological agents can include, but are notlimited to, trapidil, trapidil derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF-derivatives, orcombinations thereof; however other or additional biological agents canbe used. The one or more biological agents used to form the mound canprovide a burst of biological agent in the interior of a body passagewayand/or the body passageway itself during and/or after insertion of thestent in the body passageway; however, this is not required. As can beappreciated, a layer of one or more polymers can be coated on the mound;however, this is not required. The polymer layer can be used to controlthe release rate of the one or more biological agents from the mound;however, this is not required. The polymer layer can also oralternatively provide protection to the mound structure; however, thisis not required. When the mound includes and/or is coated with one ormore polymers, such polymers can include, but are not limited to,parylene, parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers.

Referring now to FIG. 12, the novel metal alloy 40 of stent 20 includesone or more needles or micro-needles 300. The one or more needles ormicro-needles are formed on the surface of the novel metal alloy. Theone or more needles or micro-needles are formed from one or morepolymers 312. As can be appreciated, the one or more needles ormicro-needles also or alternatively be formed from one or morebiological agents and/or adhesives. The polymer can be porous,non-porous, biodegradable and/or biostable. Polymers that can be used toat least partially form the one or more needles or micro-needlesinclude, but are not limited to, Non-limiting examples of one or morepolymers that can be used include, but are not limited to, parylene,parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA,PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesepolymers; however, other or additional polymers can be used. One or morepolymer layers 310 are coated on the top of the one or more needles ormicro-needles. As can be appreciated, layer 310 also or alternatively beformed from one or more biological agents and/or adhesives. The one ormore polymer layers 310 can include one or more polymers. Layer 310 caninclude one or more porous polymer and/or non-porous polymers. Layer 310can include one or more biostable and/or biodegradable polymers. The oneor more polymers can include, but is not limited to, parylene, paryleneC, parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA,PEG, chitosan and/or derivatives of one or more of these polymers;however, other or additional polymers can be used. The one or morepolymers that form the layer 310 can be the same or different from theone or more polymers that form the one or more needles or micro-needles300. Layer 310 can be used to 1) provide protection to the structure ofthe one or more needles or micro-needles 300, 2) at least partiallycontrol a rate of degradation of the one or more needles ormicro-needles 300, and/or 3) at least partially control a rate ofrelease of one or more biological agents on and/or in the one or moreneedles or micro-needles 300. As can be appreciated, layer 310 can haveother or additional functions. The surface of the layer 310 can be orinclude one or more layers of one or more biological agents to provide aburst of biological agent in the interior of a body passageway and/or inthe body passageway itself during and/or after insertion of the stent;however, this is not required. The one or more biological agents thatcan be used can include, but are not limited to, trapidil, trapidilderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof; however other oradditional biological agents can be used.

Referring now to FIG. 13, the base structure 40 of stent 20 includes oneor more needles or micro-needles 350. The one or more needles ormicro-needles are formed on the surface of the base structure. The oneor more needles or micro-needles are formed from one or more biologicalagents and/or one or more polymer 360. A layer 362 of biological agentand/or polymer is also formed on the surface of the base structure. Inone non-limiting example, the one or more needles or micro-needles 350are formed from one or more biological agents that include trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Inthis non-limiting example, layer 362 is also formed from one or morebiological agents that include trapidil, trapidil derivatives, taxol,taxol derivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. As can be appreciated, the one ormore biological agents in layer 362 and forming the one or more needlesor micro-needles 350 can be the same or different. The use of one ormore biological agents to coat the top surface of the base structureand/or to form one or more needles or micro-needles can provide a burstof one or more biological agent in the treatment area (e.g., bodypassageway, etc.) after insertion of the stent. In another non-limitingexample, the one or more needles or micro-needles 350 are formed fromone or more biological agents that include trapidil, trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. In thisnon-limiting example, layer 362 is formed from one or more polymers. Thepolymer layer can include one or more polymers. The polymer layer caninclude one or more porous polymers and/or non-porous polymers, and/orone or more biostable and/or biodegradable polymers. Non-limitingexamples of one or more polymers that can be used include, but are notlimited to, parylene, parylene C, parylene N, parylene F, PLGA, PEVA,PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of oneor more of these polymers. When the one or more polymers are non-porouspolymers, the one or more non-porous polymers can include, but are notlimited to, parylene C, parylene N, parylene F and/or a parylenederivative. The use of one or more biological agents to form one or moreneedles or micro-needles can provide a burst of one or more biologicalagent in the treatment area (e.g., body passageway, etc.) afterinsertion of the stent. In still another non-limiting example, the oneor more needles or micro-needles 350 are formed from one or morepolymers. The polymer layer can include one or more polymers. Thepolymer layer can include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. When the one or morepolymers are non-porous polymers, the one or more non-porous polymerscan include, but are not limited to, parylene C, parylene N, parylene Fand/or a parylene derivative. In this non-limiting example, layer 362 isformed from one or more biological agents that include trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Theuse of one or more biological agents to form layer 362 can provide aburst of one or more biological agent in the treatment area (e.g., bodypassageway, etc.) after insertion of the stent; however, this is notrequired.

Referring now to FIG. 14, the base structure 40 of stent 20 includes oneor more needles or micro-needles 400. The one or more needles ormicro-needles are formed on the surface of the base structure. The oneor more needles or micro-needles are formed from one or more biologicalagents and one or more polymers 410. A layer 412 of biological agentand/or polymer is also formed on the surface of the base structure. Ascan be appreciated, the composition of layer 412 and forming thecomposition of the one or more needles or micro-needles 400 can be thesame or different. In one non-limiting example, the one or morebiological agents that at least partially form layer 412 and/or the oneor more needles or micro-needles 400 include trapidil, trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. The one or morepolymers that at least partially form layer 412 and/or the one or moreneedles or micro-needles 400 can include one or more porous and/ornon-porous polymers, and/or one or more biostable and/or biodegradablepolymers. Non-limiting examples of one or more polymers that can be usedinclude, but are not limited to, parylene, parylene C, parylene N,parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosanand/or derivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that at least partially form layer 412and/or the one or more needles or micro-needles 400 include a non-porouspolymer to at least partially control a rate of release by moleculardiffusion of the one or more biological agents that are mixed with thepolymer. The inclusion of one or more biological agents in the one ormore needles or micro-needles can provide controlled release ofbiological agent in the treatment area (e.g., body passageway, etc.)after insertion of the stent; however, this is not required. The use ofone or more biological agents to form layer 412 and/or one or moreneedles or micro-needles 400 can provide a burst of one or morebiological agent in the treatment area (e.g., body passageway, etc.)after insertion of the stent; however, this is not required.

Referring now to FIG. 15, FIG. 15 is a modification of the arrangementillustrated in FIG. 13. In FIG. 15, a coating 470, that is formed of oneor more polymers and/or biological agents is placed over one or moreneedles or micro-needles 450 and layer 462. Specifically, the basestructure 40 of stent 20 includes one or more needles or micro-needles450. The one or more needles or micro-needles are formed on the surfaceof the base structure. The one or more needles or micro-needles areformed from one or more biological agents and/or polymers 460. A layer462 of biological agent and/or polymer is also formed on the surface ofthe base structure. The composition of layer 462 and one or more needlesor micro-needles can be the same or different. In one non-limitingexample, the one or more biological agents that can at least partiallyform layer 462 and/or one or more needles or micro-needles 450 includetrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Theone or more polymers that can at least partially form layer 462 and/orone or more needles or micro-needles include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. In onenon-limiting example, the one or more polymers that can at leastpartially form layer 462 and/or one or more needles or micro-needles 450include one or more non-porous polymer such as, but not limited to,parylene C, parylene N, parylene F and/or a parylene derivative. The oneor more non-porous polymers can be used to at least partially control arate of release by molecular diffusion of the one or more biologicalagents in layer 462 and/or in the one or more needles or micro-needles450; however, this is not required. Layer 470 that is coated on the topof the one or more needles or micro-needles and layer 462 includes oneor more biological agents and/or polymers. In one non-limiting example,the one or more biological agents that can at least partially form layer470 include trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. In one non-limiting example, the one or morepolymers that can at least partially form layer 470 include one or moreporous and/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. When theone or more polymers include one or more non-porous polymers, suchnon-porous polymer can include, but not limited to, parylene C, paryleneN, parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 462,layer 470 and/or in the one or more needles or micro-needles 450;however, this is not required. When one or more biological agents atleast partially form layer 470 and/or are coated on layer 470, notshown, the one or more biological agents can provide a burst of one ormore biological agent in the treatment area (e.g., body passageway,etc.) after insertion of the stent; however, this is not required.

Referring now to FIG. 16, FIG. 16 is a modification of the arrangementillustrated in FIG. 12. In FIG. 16, a coating 520, that is formed of oneor more polymers and/or biological agents is placed over one or moreneedles or micro-needles 500 and layer 512. The composition of layer 520and layer 512 and/or one or more needles or micro-needles can be thesame or different. Specifically, the base structure 40 of stent 20includes one or more needles or micro-needles 500. The one or moreneedles or micro-needles are formed on the surface of the basestructure. The one or more needles or micro-needles are formed from amixture of one or more biological agents and one or more polymers 510. Alayer 512 of biological agent and polymer is also formed on the surfaceof the base structure. As can be appreciated, layer 512 and/or one ormore needles or micro-needles 500 can be formed only of one or morepolymers or one or more biological agents. The composition of layer 512and one or more needles or micro-needles 500 can be the same ordifferent. In one non-limiting example, the one or more biologicalagents that can at least partially form layer 512 and/or one or moreneedles or micro-needles 500 include trapidil, trapidil derivatives,taxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The one or more polymers that canat least partially form layer 512 and/or one or more needles ormicro-needles 500 include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that can at least partially form layer512 and/or one or more needles or micro-needles 500 include one or morenon-porous polymers such as, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 512and/or in the one or more needles or micro-needles 500; however, this isnot required. In one non-limiting example, the one or more polymers thatcan at least partially form layer 520 include one or more porous and/ornon-porous polymers, and/or one or more biostable and/or biodegradablepolymers. Non-limiting examples of one or more polymers that can be usedinclude, but are not limited to, parylene, parylene C, parylene N,parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosanand/or derivatives of one or more of these polymers. When the one ormore polymers include one or more non-porous polymers, such non-porouspolymer can include, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 512,layer 520 and/or in the one or more needles or micro-needles 500;however, this is not required. When one or more biological agents atleast partially form layer 520 and/or are coated on layer 520, notshown, the one or more biological agents can provide a burst of one ormore biological agent in the treatment area (e.g., body passageway,etc.) after insertion of the stent; however, this is not required.

Referring now to FIG. 17, FIG. 17 is another modification of thearrangement illustrated in FIG. 12. In FIG. 17, one or more internalchannels 570 are formed in one or more needles or micro-needles 550. Theone or more internal channels 570 can include one or more biologicalagent and/or polymers. Specifically, the base structure 40 of stent 20includes one or more needles or micro-needles 550. The one or moreneedles or micro-needles are formed on the surface of the basestructure. The one or more needles or micro-needles are formed from oneor more polymers and/or biological agents 560. A layer 562 of polymerand/or biological agent is also formed on the surface of the basestructure. The composition of layer 562 and one or more needles ormicro-needles can be the same or different. The one or more polymersthat can at least partially form layer 562 and/or one or more needles ormicro-needles 550 include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that can at least partially form layer562 and/or one or more needles or micro-needles 550 include one or morenon-porous polymers such as, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 562,in the one or more needles or micro-needles 550, and/or in one or moreinternal channels 570; however, this is not required. One or more of theneedles or micro-needles 550 include an internal channel 570. Theinternal channel is illustrated as including one or more biologicalagents 580; however, it can be appreciated that one or more channels caninclude a mixture of one or more polymers and/or biological agents, oronly one or more polymers. In one non-limiting example, the one or morebiological agents includes trapidil, trapidil derivatives, taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The top opening of the channelenables delivery of one or more biological agents directly intotreatment area (e.g., a wall of a body passageway or organ, etc.). Theone or more biological agents in internal channel 570 can pass throughand/or molecularly diffuse through the one or more polymers that atleast partially form the one or more needles or micro-needles; however,this is not required. The release of the one or more biological agentsthrough the one or more polymers that at least partially form the one ormore needles or micro-needles can be a controlled or an uncontrolledrelease rate. As can be appreciated, a layer of biological agent, notshown, can be coated one or more needles or micro-needles 550. The layerof biological agent could include one or more biological agents. Theplacement of the layer of biological agent on the one or more needles ormicro-needles 550 can provide a burst of one or more biological agentsin the treatment area; however, this is not required. As can beappreciated, other combinations of polymer layer and/or layer ofbiological agent can be used on the stent. As can also or alternativelybe appreciated, a layer of polymer, not shown, can be coated one or moreneedles or micro-needles 550. The layer of polymer could include one ormore polymers. The placement of the layer of polymer on the one or moreneedles or micro-needles 550 can be used to a) at least partiallycontrol a release rate of one or more biological agents from the stent,and/or 2) provide structural support and/or protection to one or moreneedles or micro-needles. As can be appreciated, the polymer layer, whenused, can have other or additional functions. These other combinationsare also encompassed within the scope of the present invention.

Referring now to FIG. 18, there is illustrated an enlarged portion of asurface of a stent 20 which includes a surface needle, micro-needle orother type of structure or micro-structure 600. The needle is shown toinclude at least one biological agent 610; however, the needle can alsoor alternatively include one or more polymers, adhesives, etc. Thestent, when in the form of a stent, is illustrated as being in anexpanded state. When the stent is inserted or expanded in a treatmentarea, the needle 600 on the outer surface of the stent engages and/or atleast partially penetrates into blood vessel or organ V. When the needleincludes one or more biological agents, the one or more biologicalagents are at least partially locally applied to a treatment area. Thiscan be a significant advantage over system wide treatment with one ormore biological agents. The locally treatment with one or morebiological agent via the needle can more effectively and/or efficientlydirect the desired agents to a treated area. The release of one or morebiological agents from the needle can be controlled, if desired, todirect the desired amount of one or more biological agents to a treatedarea over a desired period of time. When the stent is expanded in ablood vessel, the one or more needles enable local delivery of one ormore biological agents into the wall of the blood vessel. This localdelivery is especially advantageous in large and/or thick blood vesselswherein system wide drug treatment is not very effective. In addition,the local delivery of biological agent by the needle directly into theblood vessel can be more effective than only releasing the biologicalagent from the surface of the stent since diffusion from the surface ofthe stent to the larger and/or thicker blood vessel may not be aseffective as direct delivery by the needles to the blood vessel. The oneor more needles on the stent surface can also or alternatively be usedto facilitate in securing the stent to the treatment area during theexpansion and/or insertion of the stent in a treatment area.

It will thus be seen that the objects set forth above, among those madeapparent from the preceding description, are efficiently attained, andsince certain changes may be made in the constructions set forth withoutdeparting from the spirit and scope of the invention, it is intendedthat all matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense. The invention has been described with reference topreferred and alternate embodiments. Modifications and alterations willbecome apparent to those skilled in the art upon reading andunderstanding the detailed discussion of the invention provided herein.This invention is intended to include all such modifications andalterations insofar as they come within the scope of the presentinvention. It is also to be understood that the following claims areintended to cover all of the generic and specific features of theinvention herein described and all statements of the scope of theinvention, which, as a matter of language, might be said to falltherebetween.

1. A medical device that is at least partially formed of a metal alloywhich improves the strength and ductility of the medical device, saidmetal alloy including at least about 95 weight percent of a solidsolution, said metal alloy including 45-50 weight percent rhenium and50-55 weight percent molybdenum, said metal alloy including carbon andoxygen and having a carbon to oxygen atomic ratio of at least about 2:1,said metal alloy having a nitrogen content of less than about 20 ppm, acarbon content of less than about 150 ppm, and an oxygen content of lessthan about 50 ppm, said metal alloy having an average yield strength ofat least about 98 ksi and an average ultimate tensile strength of atleast about 100 ksi, said metal alloy having an average grain size ofover 5 ASTM, said metal alloy having an average tensile elongation of atleast about 25% said metal alloy having a carbon to nitrogen atomicratio of less than about 40:1 and an oxygen to nitrogen atomic ratio ofless than about 30:1, at least one region of said medical deviceincludes at least one biological agent.
 2. The medical device as definedin claim 1, wherein said metal alloy including at least about 99 weightpercent of a solid solution, said solid solution including at least 95weight percent rhenium and molybdenum and an additional metal, saidadditional metal constituting less than about 2 weight percent of saidsolid solution said additional metal selected from the group consistingof titanium, yttrium, zirconium, or mixtures thereof.
 3. The medicaldevice as defined in claim 1, wherein said metal alloy metal alloyincludes a plurality of second phase particles, said second phaseparticles including carbides, carbo-nitrides, oxides or mixturesthereof.
 4. The medical device as defined in claim 1, wherein said metalalloy has an average grain size of over 5-10 ASTM.
 5. The medical deviceas defined in claim 1, wherein said metal alloy has an average densityof at least 13 gm/cc.
 6. The medical device as defined in claim 1,wherein said metal alloy includes about 46-49 weight percent rhenium andabout 51-54 weight percent molybdenum.
 7. The medical device as definedin claim 1, wherein said medical device is a stent, graft, valve, screw,nail, rod, PFO device, prosthetic device, sheath, guide wire, ballooncatheter, hypotube, catheter, electrophysiology catheter, staple orcutting device.
 8. The medical device as defined in claim 1, whereinsaid at least one biological agent includes trapidil, trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, GM-CSF, GM-CSF derivatives, and combinations thereof. 9.The medical device as defined in claim 1, wherein at least one region ofsaid medical device includes at least one polymer.
 10. The medicaldevice as defined in claim 9, wherein said at least one polymer at leastpartially coats said at least biological agent, encapsulates said atleast biological agent, and combinations thereof.
 11. The medical deviceas defined in claim 10, wherein said at least one polymer controllablyreleases at least one of said biological agents.
 12. The medical deviceas defined in claim 9, wherein said at least one polymer includesparylene, a parylene derivative, chitosan, a chitosan derivative, PLGA,a PLGA derivative, PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA,a PBMA derivative, POE, a POE derivative, PGA, a PGA derivative, PLLA, aPLLA derivative, PAA, a PAA derivative, PEG, a PEG derivative, orcombinations thereof.
 13. The medical device as defined in claim 1,wherein said medical device includes at least one micro-structure in anouter surface of said medical device.
 14. The medical device as definedin claim 13, wherein said at least one micro-structure is at leastpartially formed of, includes, or combinations thereof, a materialconsisting of a polymer, a biological agent, or combinations thereof.15. The medical device as defined in claim 2, wherein said metal alloymetal alloy includes a plurality of second phase particles, said secondphase particles including carbides, carbo-nitrides, oxides, and mixturesthereof.
 16. The medical device as defined in claim 15, wherein saidmetal alloy has an average grain size of about 5-10 ASTM.
 17. Themedical device as defined in claim 16, wherein said metal alloy has anaverage density of at least 13 gm/cc.
 18. The medical device as definedin claim 17, wherein said metal alloy includes about 46-49 weightpercent rhenium and about 51-54 weight percent molybdenum.
 19. Themedical device as defined in claim 18, wherein at least one region ofsaid medical device includes at least one polymer, said at least onepolymer at least partially cost said at least biological agent,encapsulates said at least biological agent, and combinations thereof.20. The medical device as define in claim 19, wherein said at least onepolymer controllably releases at least one of said biological agents.21. The medical device as defined in claim 18, wherein said medicaldevice includes at least one micro-structure in an outer surface of saidmedical device.
 22. The medical device as defined in claim 21, whereinsaid at least one micro-structure is at least partially formed of,includes, or combinations thereof, a material consisting of a polymer, abiological agent, and combinations thereof.
 23. The medical device asdefined in claim 1, wherein said solid solution includes by weightpercent: C ≦150 ppm Mo 50-55% O ≦100 ppm N ≦40 ppm Re 45-50% Ti ≦0.5% Y≦0.1% Zr ≦0.25%.


24. The medical device as defined in claim 17, wherein said solidsolution includes by weight percent: C ≦150 ppm Mo 50-55% O ≦100 ppm N≦40 ppm Re 45-50% Ti ≦0.5% Y ≦0.1% Zr ≦0.25%


25. The medical device as defined in claim 1, wherein said metal alloyincluding carbon and oxygen and having a carbon to oxygen atomic ratioof about 2.5-10:1.
 26. The medical device as defined in claim 18,wherein said metal alloy including carbon and oxygen and having a carbonto oxygen atomic ratio of about 2.5-10:1.
 27. The medical device asdefined in claim 1, wherein said metal alloy has an average grain sizeof about 6-9 ASTM.
 28. The medical device as defined in claim 18,wherein said metal alloy has an average grain size of about 6-9 ASTM.29. The medical device as defined in claim 1, wherein said atomic ratioof carbon to oxygen in said metal alloy is less than about 50:1.
 30. Themedical device as defined in claim 18, wherein said atomic ratio ofcarbon to oxygen in said metal alloy is less than about 50:1.
 31. Themedical device as defined in claim 1, wherein said metal alloy includestitanium.
 32. The medical device as defined in claim 18, wherein saidmetal alloy includes titanium.
 33. The medical device as defined inclaim 31, wherein said metal alloy includes titanium and zirconium, saidtitanium and zirconium having a weight ratio of about 1.2-5:1.
 34. Themedical device as defined in claim 32, wherein said metal alloy includestitanium and zirconium, said titanium and zirconium having a weightratio of about 1.2-5:1.